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Histology and
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Histopathology
From Cell Biology to Tissue Engineering
Review
Summary. We review the morpho-functional basis of sprouting phase, encompassing EC migration (concept
the different types of angiogenesis and report our and characteristics of endothelial tip cells, tip cell
observations, including the formation of angiogenesis- selection, lateral inhibition, localized filopodia
related secondary structures. First of all, we consider the formation, basal lamina degradation and extracellular
following issues: a) conceptual differences between changes facilitating EC migration), EC proliferation
angiogenesis and vasculogenesis, b) incidence of (concept of endothelial stalk cells), pericyte
angiogenesis in pre- and postnatal life, c) regions of mobilization, proliferation, recruitment and changes in
vascular tree with angiogenic capacity, d) cells CD34+ adventitial stromal cells and inflammatory cells,
(endothelial cells, pericytes, CD34+ adventitial stromal tubulogenesis, formation of a new basal lamina, and
cells of the microvasculature and inflammatory cells) vascular anastomosis with capillary loop formation, and
and extracellular matrix components involved in c) vascular remodelling and stabilization phase (concept
angiogenesis, e) events associated with angiogenesis, f) of phalanx cells). Subsequently, the concept, incidence,
different types of angiogenesis, including sprouting and events and mechanisms are considered in the other forms
intussusceptive angiogenesis, and other angiogenic or of angiogenesis. Finally, we contribute the formation of
vascularization forms arising from endothelial precursor postnatal angiogenesis-related secondary structures: a)
cells (postnatal vasculogenesis), vasculogenesis intravascular structures through piecemeal angiogenesis,
mimicry, vessel co-option and piecemeal angiogenesis. including intravascular papillae in vessel tumours and
Subsequently, we consider the specific morpho- pseudotumours (intravascular papillary endothelial
functional characteristics of each type of angiogenesis. hyperplasia, vascular transformation of the sinus in
In sprouting angiogenesis, we grouped the events in lymph nodes, papillary intralymphatic angioendo-
three phases: a) activation phase, which includes thelioma or Dabska tumour, retiform hemangio-
vasodilation and increased permeability, EC, pericyte endothelioma, hemangiosarcoma and lymphangio-
and CD34+ adventitial stromal cell activation, and sarcoma), vascular septa in hemorrhoidal veins and
recruitment and activation of inflammatory cells, b) intravascular projections in some tumours; b) arterial
intimal thickening; c) intravascular tumours and
Offprint requests to: Lucio Díaz-Flores, Departamento de Ciencias pseudotumours (e.g. intravenous pyogenic granulomas
Médicas Básicas, Facultad de Medicina, Universidad de La Laguna, and intravascular myopericytoma); d) vascular
Tenerife, Spain. e-mail: kayto54@gmail.com glomeruloid proliferations; and e) pseudopalisading
DOI: 10.14670/HH-11-923 necrosis in glioblastoma multiform.
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Angiogenesis and related secondary structures
Fig. 1. Angiogenesis in pre- (A) and postnatal (B and C) life. A. An embryonic sprouting vessel (arrow) originating from a vasculogenic vessel (vv). B.
A sprouting vessel (arrow) originating from a postcapillary venule (pv) in the adipose tissue. C. A sprouting vessel (arrow) originating from the rat
femoral vein (fv) induced by peri-venous administration of PGE2 and glycerol. D. Size of the rat femoral artery (black asterisk) and vein (white asterisk)
(scale in mm). Scale bars: A, 20 µm; B, 15 µm; C, 10 µm.
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Angiogenesis and related secondary structures
Fig. 3. Phenomena in the activation phase of angiogenesis. A. A dilated and congestive capillary between oedematous spaces. Note perivascular
activated CD34+ adventitial stromal cells (arrows). B. Ultrastructural image of the opening of the interendothelial junctions (arrow). C. Demonstration of
vascular permeability during angiogenesis. Under electron microscopy, Monastral Blue particles (asterisk) are observed between endothelial cells (ec)
and pericytes (p) in a leaky vessel. D. A dilated vessel showing early migration of leukocytes (L) between an opened interendothelial cell junction
(arrow). Note an activated CD34+ adventitial stromal cell (sc) with a nucleus increased in size and with a prominent nucleolus. E. Portion of an
activated mast cell with degranulation between a process of a stromal cell (sc) and pericytes (p). Endothelial cell: ec). Scale bars: A, 25 µm; B, D, E, 1
µm; C, 2 µm.
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Angiogenesis and related secondary structures
Fig. 4. EC migration in sprouting phase. A. An endothelial tip cell (tc), devoid of basement membrane, is observed in an angiogenic vessel. Note
numerous free polyribosomes and abundant filaments. In the insert, an image under light microscopy of a migrating CD34-stained EC. B. Migrating
CD34+ ECs with projections in their tips (arrows). C. Double stained microscopic section with anti-CD34 (staining endothelial cells - brown) and anti-
αSMA (staining pericytes - red). Note the absence of pericytes around the migrating and neighbouring ECs (arrow). Scale bars: A, 1 µm; B, C, 14 µm.
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Angiogenesis and related secondary
Fig. 5. Endothelial
stalk cells in
sprouting phase of
angiogenesis.
A, B. Vascular
sprouts (arrows) are
observed in double
stained sections with
anti-CD34 (staining
endothelial stalk cells
- brown) and anti-
αSMA (staining
pericytes - red). Note
in A that sprouts
originate from one
side of the parent
vessels, probably
leading to angiogenic
stimulation.
C. Ultrastructural
image of endothelial
stalk cells (ec)
around a narrow or
virtual lumen (L).
Interendothelial cell
junctions (arrows)
and a mitotic
endothelial stalk cell
are observed. Also
note developing
basement
membrane, a
perivascular cell (p)
and projections of
perivascular cells.
Observe the contacts
between the
perivascular cell and
endothelial stalk
cells. Insert 1: Detail
of the interendothelial
cell junctions
(arrows). Insert 2:
Pericytes (stained in
red with anti-αSMA)
and endothelial stalk
cells (stained in
brown with anti-
CD34) under light
microscopy. Scale
bars: A, 20 µm; B, 30
µm; C, 2 µm.
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Angiogenesis and related secondary
Fig. 6. Perivascular CD34+ stromal cell and macrophage behaviour, and tubulogenesis in sprouting phase of angiogenesis. A. One CD34+
perivascular stromal cell in mitosis (arrow) around a microvessel (asterisk). B. Double staining with anti-ki67 and anti-CD34 reveals ki-67 expression in
nuclei of CD34+ perivascular stromal cells (arrows). C. Double staining with anti-CD34 (brown) and anti-αSMA (red) shows stromal cells expressing
either CD34 or αSMA. D. Double staining with anti-CD68 (staining macrophages – red) and anti-CD34 (staining stromal cells – brown) reveal
association between macrophages and stromal cells. E. Ultrastructural image of vascular lumen formation (tubulogenesis) (asterisks) between
endothelial stalk cells (ec). Pericyte: p. Scale bars: A, 10 µm; B, 15 µm; C, 25 µm; D, 20 µm; E, 1 µm.
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Angiogenesis and related secondary
Initially, active ECs secrete matrix-degrading 7.1.4.2. Phase of vascular remodelling and
enzymes, such as plasminogen activator and collagenase, stabilization
causing fragmentation of the basement membrane (see
above). Thus, in the initial stages of the developing We have considered three main phases in
microvessels, fibronectin is a predominant component of angiogenesis for a better understanding of this process,
the provisional matrix, making up a delicate fibrillary although the phenomena in each phase overlap with the
network. Fibrils of type IV and V collagen, patchy next. Thus, most vascular remodelling and stabilization
amorphous deposits of laminin and rare to absent fibrils phenomena initiate in the sprouting phase (see above).
of type I and III collagen have also been described in Therefore, in this section, we address only the most
outstanding phenomena in this final phase of
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Angiogenesis and related secondary
Fig. 7. Sprouting angiogenesis: vascular anastomosis, remodelling and stabilization. A. Double staining showing CD34+ endothelial cells (brown)
anastomosing to (arrow) microvessels (v) with periendothelial αSMA+ mural cells (red). B, C. Ultrastructural images in which regressing vessels with
EC degenerative phenomena (B) (arrow) and with intravascular accumulations of platelets (C) are observed. D. Orderly arrangement of phalanx
endothelial cells (ec), which show a sessile morphology. Mural cells: mc. Scale bars: A, 15 µm; B-D, 2 µm.
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Angiogenesis and related secondary
angiogenesis.
(Fig. 7C). We have hypothesized that this accumulation
7.1.4.2.1. Vascular remodelling. During angiogenesis, a of factor-releasing platelets during the massive
dense network of neovessels is generally created and is regression of neocapillaries may convert highly
followed by a process of remodelling, in which many vascularized zones (as occurs in granulation tissue) into
vessels undergo involution and branching remodelling. a ‘paracrine transitional organ’, facilitating fibroblast/
In this mechanism, pruning of excessive blood vessels is myofibroblast proliferation (Díaz-Flores et al., 2009b).
essential. Two different types of pruning have been Subsequently, homogenized platelets, endothelial cell
described, depending on whether vessels are lumenized debris and basement membrane residues are observed in
or not (Kochhan et al., 2013; Franco et al., 2015; Lenard the regions affected by vascular remodelling. This
et al., 2015; Betz et al, 2016). When vessels are massive regression of capillaries originates capillary-free
lumenized, pruning involves cell-self fusion (Lenard et zones and marked reduction in overall vascular density
al., 2015) and formation of a unicellular tube, in which (Benjamin et al., 1998).
the transcellular lumen collapses (vessel constriction and
occlusion), followed by apical membrane retraction and 7.1.4.2.2. Vascular maturation and stabilization.
reduction in cell-cell contacts, with EC apoptosis and/or Maturation and stabilization of persistent vessels
migration. This process is similar to intussusceptive involves maturation regulating molecules, recruitment of
angiogenesis (see below), in which intravascular pillars pericytes (see above), extracellular matrix formation,
may form in vessels originated by sprouting and vessel type (arteries, arterioles, capillaries, venules
angiogenesis (Djonov et al., 2001; Makanya et al., 2005; and veins) and organ-specific differentiation. Maturation
Hlushchuk et al., 2011). In non-lumenized vessel regulating molecules include angiopoietins and PDGFs
pruning, cell rearrangements occur with formation of a (Potente et al., 2011). Pericytes act in vessel stabilization
unicellular bridge, followed by apical compartment by the release of stabilizing factors including
separation, a reduction in cell-cell contacts, EC angiopoietin-1 and TMP3 (Suri et al., 1996).
apoptosis and/or migration and detachment of the vessel. Angiopoietin-1 induces DLL4 expression through TIE2-
In both types of pruning, residual ECs may migrate and receptor. DLL4 activates Notch signalling which down-
return to neighbouring vessels by a reverse sprouting regulates VEGRF2, thereby preventing further sprouting
mechanism (Chen et al., 2012; Udan et al., 2013). and inducing the expression of NRARP, which enhances
Elevated levels of oxygen, low VEGF levels, WNT signalling, increasing tight junction stabilization.
angiopoietin II signals and vessel flow changes play an In addition, pericytes stimulate vascular basal membrane
important role in vascular pruning (Claxton and formation (Stratman et al., 2009) (see above). Likewise,
Fruttiger, 2005; Lange et al., 2009; Hlushchuk et al., pericytes prevent regression by releasing inhibitors of
2011). Indeed, pruning involves EC apoptosis (Fig. 7B) metalloproteinases (e.g. tissue inhibitor of
(high oxygen level—Lange et al., 2009—and metalloproteinase 3). However, there are apparently
macrophage through WNT7b—Lobov et al., 2005— conflicting data in the role of pericytes in vessel
induced apoptosis), endothelial migration-dependent stabilization (von Tell et al., 2006). Although pericyte
regression (apoptosis-independent vascular regression) coating may prevent vessel regression (Benjamin et al.,
(Dimmeler and Zeiher, 2000; Wietecha et al., 2013) and 1998), pericytes have been observed in immature,
‘reverse intussusception’ (intussusceptive vascular mature and involutive microvessels (Díaz-Flores et al.,
pruning) (Hlushchuk et al., 2011) (for review: Ricard 1991; Inai et al., 2004). Moreover, pericyte-like cells
and Simons, 2015). Intraluminal flow changes (flow persist in some involutive vessels presenting EC
level, orientation and periodicity) also regulate cellular apoptosis.
rearrangement during blood vessel pruning and
branching remodelling, in which the axial polarity Concept of phalanx cells
between the Golgi and nucleus of ECs determines
polarized EC migration (Le Noble et al., 2004; Lee et al, During vessel maturation and stabilization, ECs may
2011; Chen et al., 2012; Tirziu et al., 2012; Kochhan et adopt a thickly apposed, orderly cobblestone-like
al., 2013; Udan et al., 2013; García and Larina, 2014; appearance, acquiring a more sessile cell fate (Fig. 7D)
Lenard et al., 2015; Franco et al., 2015; Ricard and and acquiescent phenotype, as well as the capacity to
Simons, 2015) Thus, it has been proposed that EC sense and regulate perfusion, and to inhibit metastasis in
migration and incorporation into high-flow segments tumours (De Bock et al., 2009; Mazzone et al., 2009). In
depend on Notch pathway signalling (Phng et al., 2009) this stage, these cells are known as endothelial phalanx
and low blood flow, resulting in a smaller total vessel cells, since their alignment and characteristics resemble
area and an increase in blood flow. Alternatively, EC those of ancient Greek soldiers forming military
apoptosis and intussusceptive regression are triggered by phalanxes.
low VEGF levels, resulting in lower blood flow and a
smaller total vessel area (Ricard and Simons, 2015; 7.2. Intussusceptive angiogenesis
Lenard et al., 2015; Franco et al., 2015).
Involutive vessels may also show marked 7.2.1. Definition and nomenclature
intravascular accumulation of platelets (platelet thrombi)
Intussusceptive angiogenesis is the process by which
pre-existing vessels split or remodel through the
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Angiogenesis and related secondary
Fig. 8. Intussusceptive, mimicry and co-option forms of vascularization. A. In double staining with anti-CD34 (staining ECs: brown) and anti-αSMA
(staining pericytes: red), an endothelial pillar (transcapillary interendothelial bridge) is observed (arrow). B, insert. ultrastructural images of cross-
sectioned pillars (arrows), covered by endothelial cells -ec-, and with central core formation (presence of collagen fibres -co). C. channels containing
red cells and lined with melanotic cells and some melanophages (vascular mimicry) in a melanoma. D. observe connection between endothelial-lined
vasculature (elv) and a channel lined with melanotic cells (clm), and with red cells in its lumen. E. melanotic cells forming cuff around vessels (arrows)
are observed in a melanoma (co-option form of vascularization). Scale bars: A, C-E, 25 µm; B, 1 µm.
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Angiogenesis and related secondary
7.3.3. Events and mechanisms in angiogenesis Vasculogenic mimicry or vascular mimicry is the
with EPC participation generation of perfusable, non-endothelial-lined tube-like
or channel structures, which are generally formed by: a)
The principal events in angiogenesis in which EPCs highly plastic migratory/invasive tumour cells that
participate are as follows: a) EPC release from the bone upregulate endothelial-selective markers, and b)
marrow niche, and incorporation into the blood remodelled PAS+ extracellular matrix on the inner wall
(circulating EPCs), b) recruitment and integration within of the tube-like structures (Maniotis et al., 1999; Paulis
angiogenic vasculature (incorporation into the vascular et al., 2010). The network formed by these structures is
endothelium of EPCs) and c) differentiation into mature connected with or adjacent to blood vessels, transporting
ECs. blood or fluid from connecting or adjacent leaky vessels,
7.3.3.1. Release of EPCs and incorporation into the respectively (Maniotis et al., 1999; Paulis et al., 2010).
blood Therefore, the networks of channels originated by
vascular mimicry may form part of the complex
This phase includes detachment of c-kit positive vasculature in certain tumours, in which all the types of
cells from their niches, movement of EPCs to the angiogenesis described here participate (sprouting and
vascular zone and incorporation in the circulation intussusceptive angiogenesis, postnatal vasculogenesis
(Heissig et al., 2002). In general, several factors, by precursor ECs, vessel co-option and vascular
mimicry) (Döme et al., 2007; Hillen and Griffioen,
2007;
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Angiogenesis and related secondary
The most important findings in vascular channels are Vessel co-option is the process by which tumour
those related to tumour cells (Fig. 8C) and extracellular cells grow using pre-existing vessels (tumour cells co-
matrix. Tumour cells involved in vascular mimicry opt host vessels). Therefore, this process is not a true
exhibit high plasticity and down-regulation of the angiogenic mechanism, since the neoplasic cells grow
original phenotype markers, showing some over and along vessels (tumour cells parasitize on the
characteristics of embryonic progenitors and ECs pre-existing vasculature).
(Bittner et al., 2000; Seftor et al., 2002; Zhang et al.,
2007; Paulis et al., 2010). Moreover, these tumour cells 7.5.2. Incidence
have anti-coagulant properties and act in matrix
remodelling, providing a perfusion pathway. Thus, in Tumours in well-vascularized organs, such as the
melanoma, the tumour cells that form vascular channels lung and brain, can be a substrate for this type of growth
show down-regulation of genes related to a melanocytic (Wesseling et al., 1994; Pezzella et al., 1997), mainly
phenotype (e.g. tyrosinase and melan A) (Demou and during initial tumour phases. This process has been
Hendrix, 2008), while expression of endothelium- described in glioblastoma, melanoma, Kaposi sarcoma,
associated genes occurs (e.g. CD34, CD105, neurophilin and in a model of neuroblastoma, non-small cell
1, E-selectin, VE-cadherin and tyrosine-kinase receptor carcinoma, Lewis lung carcinoma and murine ovarian
1). Extracellular matrix in the networks of tubular cancer (Pezzella et al., 1997; Holash et al., 1999; Döme
structures shows PAS positivity and presence of et al., 2002; Kim et al., 2002; Zhang et al., 2003). A
collagen IV and VI, laminin, heparan-sulphate similar mechanism has been suggested for
proteoglycans and other components. myofibroblasts during wound healing (Kilarski et al.,
2009), although this finding may be the expression of
7.4.4. Mechanisms differentiating precursor adventitial cells (Díaz-Flores et
al., 2014). We have observed vessel co-option in
Signalling pathways in vascular mimicry are highly melanoma implanted in mice, particularly following
complex (for revision: Seftor et al., 2012). Briefly, prior radiation of the tumour bed before implantation,
hypoxia participates in tumour cell plasticity, and in human glioblastoma multiforme. In the latter, the
contributing to the phenotype switch of tumour cells growing tumour cells emit numerous processes around
(Mihic-Probst et al., 2012). VE-cadherin and EphA2, the pre-existing vessels, which follow an undulating
P13K (phosphoinositide 3 route. Subsequently, vessel regression is observed. In
– kinase) and FAK (focal adhesion kinase) play an this case, cell projections form what is described as
palisade necrosis (see below).
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Angiogenesis and related secondary
Fig. 9. Piecemeal angiogenesis in experimental conditions and in the formation of angiogenesis-related secondary structures (papillae) in vessel
tumours and pseudotumours. A. semithin section showing intravascular papillae (arrows) after PGE2 and glycerol administration around the rat femoral
vein. B. intravascular papillary endothelial hyperplasia. Numerous papillae are observed in a section stained with anti-CD34 (staining ECs: brown) and
anti-αSMA (staining mural cells: red). C. numerous papillae are also observed in a cavernous hemangioma. Note the wall of a vessel with endothelial
(brown) and mural (red) cells (arrow), as well as the papillae in the lumen. D-F. Papillae in a cavernous lymphangioma. Sections stained with
podoplanin show a linear arrangement of papillae, some of which are joined by ECs (F, arrow). Scale bars: A, 25 µm; B, C, 15 µm; D, 35 µm; E, F, 7
µm.
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Angiogenesis and related secondary
Fig. 10. Piecemeal angiogenesis in compartmentalization of hemorrhoidal veins and in vascular invasion/pseudoinvasion. A, B. images of hemorrhoidal
veins in which successive series of secondary papillae, arranged in a linear fashion (arrow) (A), form several septa (arrows) with compartmentalization
of the vein lumen (B). C. minimally invasive follicular thyroid carcinoma. Detail of an intravascular tumour gland (asterisk), encircled by CD34+
endothelium, as occurs in papillary structures. Note a gland (double asterisk) partially encircled by CD34+ endothelial cells, which originate from the
vessel wall. A and B: double staining with anti-CD34 (brown) and anti-αSMA (red). C: staining with CD34 (brown). Scale bars: A, 15 µm; B, 40 µm; C,
12 µm.
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Angiogenesis and related secondary
Vascular glomeruloid bodies have been described in Two important structures in glioblastomas are
vascular tumours (frequently associated with POEMS related to angiogenesis: pseudopalisading necrosis and
syndrome – Forman et al., 2007; Yuri et al., 2008; glomeruloid vascular structures described above.
Gonzalez-Guerra et al., 2009) and malformations of the In glioblastoma, two main types of necrosis can be
skin, in glioblastoma multiforme (Fig. 12A,B) (Rojiani observed: pseudopalisading necrosis and large necrosis.
and Dorovini-Zis, 1996), and in other tumours, including Pseudopalisading necrosis in glioblastoma is formed by
breast, lung, endometrium, prostate and meninge a garland-like arrangement of tumour cells (rim of cells)
tumours (Ohtani 1992; Bläker et al., 1999; Straume et around a central degenerative region (Fig. 12C). The
al., 2002; Goffin et al., 2003; Kandemir et al., 2014), as resulting pseudopalisades can be long and undulating or
well as in experimental conditions (e.g. after small and rosette-like. This pseudopalisading
VPF/VEGF-164 gene delivery) (Sundberg et al., 2001). configuration of astrocytic cells is essentially unique for
glioblastoma. The hypothesis of a mixed population of
8.4.3. Characteristics neoplasic and inflammatory cells to explain the
pseudopalisades is not sustainable, since practically all
In glomeruloid bodies, florid microvascular cells in this location are neoplasic astrocytic cells.
proliferation, with packed anastomosing capillaries, Currently, several authors are of the opinion that
shows prominent ECs, which express CD31 and CD34 pseudopalisades could represent an astrocytic cell
(Fig. 12A). These ECs present weak VEGF reactivity population that rapidly migrates away from a
and a Ki-67 proliferation index above 10% (Kandemir et dysfunctional vasculature (from a hypoxic zone) (Brat et
al., 2014). In addition, the pericyte population, with al., 2004; Rong et al., 2006). In pseudopalisades, we
αSMA expression, is relatively important in vessel walls have observed that neoplasic astrocytic cells emit
of glomeruloid structures (Fig. 12B). numerous processes toward an involutive vessel in the
axis of the degenerative central zone. These processes
8.4.4. Mechanisms and sequence of formation and are positive for anti-gliofibrillar acid protein (Fig. 12D
prognostic importance and E) and therefore form most of the degenerative
central zone, in which debris of CD34+ ECs of the
Experimentally, it has been demonstrated that VPF- involutive vessel are also observed (Fig. 12F). Loss of
VEGF-164 is sufficient for induction of glomeruloid pericytes or vascular smooth muscle cells occurs in these
bodies. Likewise, VPF-VEGF-164 is also necessary for vessels. Normally, astrocyte processes envelop synapses,
maintaining these vascular bodies (Sundberg et al., make contact with nodes of Ranvier, form gap junctions
2001). The sequence of glomeruloid body formation is between distal processes of other astrocytes and
as follows: a) vessel dilation and focal accumulation in establish interactions with blood vessels, where they
the vessel EC layer of plump primitive cells, which show form astrocytic endfeet. Our results (obtained in
EC markers, increased expression of VGFR-2 and lack conjunction with Spreafico MA†, nonpublished
of pericyte markers; b) the cells in the accumulations observations) agree with the concept that
proliferate and extend toward the vessel lumen and the pseudopalisades are formed by a mechanism in which
neoplasic astrocytes grow over and along a vessel, which
12
Angiogenesis and related secondary
Fig. 12. Angiogenesis in glomeruloid vascular proliferations and in pseudopalisading necrosis formation. A, B. Glomeruloid bodies with florid
microvascular proliferation, showing prominent CD34+ ECs (A) and an abundant pericyte population (B). C-F. pseudopalisading necrosis in
glioblastoma formed by a garland-like arrangement of tumour cells (rim of cells) around a central degenerative zone (cz), observed in HE (C), anti-
protein gliofibrillar acid (D, E) and in anti-CD34 stained sections. Note that the central degenerative region is formed by the gliofibrillar acid +
projections of the neoplasic astrocytic cells (D, E), which converge in a central vessel (E, arrow). F. Degenerative phenomena (residual
expression of CD34) (arrow) in a central vessel of the pseudopalisading necrosis. Scale bars: A, 20 µm; B, 15 µm; C-E, 50 µm; F, 40 µm.
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Angiogenesis and related secondary
31, 2836-2844.
D.H., Lee E.S., Kim H.K., Ryu K.W. and Bae J.M. (2003). Circulating
Hoffmann J., Feng Y., vom Hagen F., Hillenbrand A., Lin J., Erber R.,
numbers of endothelial progenitor cells in patients with gastric and
Vajkoczy P., Gourzoulidou E., Waldmann H., Giannis A., Wolburg
breast cancer. Cancer Lett. 198, 83-88.
H., Shani M., Jaeger V., Weich H.A., Preissner K.T., Hoffmann S.,
Kim M., Lee C., Payne R., Yue B.Y., Chang J.H. and Ying H. (2015).
Deutsch U. and Hammes H.P. (2005). Endothelial survival factors
Angiogenesis in glaucoma filtration surgery and neovascular
and spatial completion, but not pericyte coverage of retinal
glaucoma: A review. Surv. Ophthalmol. 60, 524-535.
capillaries determine vessel plasticity. FASEB J. 19, 2035-2036.
Kim S.O., Trau H.A. and Duffy D.M. (2017). Vascular endothelial growth
Holash J., Maisonpierre P.C., Compton D., Boland P., Alexander C.R.,
factors C and D may promote angiogenesis in the primate ovulatory
Zagzag D., Yancopoulos G.D. and Wiegand S.J. (1999). Vessel
follicle. Biol. Reprod. 96, 389-400.
cooption, regression, and growth in tumors mediated by
Kochhan E., Lenard A., Ellertsdottir E., Herwig L., Affolter M., Belting
angiopoietins and VEGF. Science 284, 1994-1998.
H.G. and Siekmann A.F. (2013). Blood flow changes coincide with
Inai T., Mancuso M., Hashizume H., Baffert F., Haskell A., Baluk P., Hu-
cellular rearrangements during blood vessel pruning in zebrafish
Lowe D.D., Shalinsky D.R., Thurston G., Yancopoulos G.D. and
embryos. PLoS One 8, e75060.
McDonald D.M. (2004). Inhibition of vascular endothelial growth
Konerding M.A., Turhan A., Ravnic D.J., Lin M., Fuchs C., Secomb
factor (VEGF) signaling in cancer causes loss of endothelial
T..W, Tsuda A and Mentzer SJ. (2010) Inflammation-induced
fenestrations, regression of tumor vessels, and appearance of
intussusceptive angiogenesis in murine colitis. Anat. Rec.
basement membrane ghosts. Am. J. Pathol. 165, 35-52.
(Hoboken). 293, 849-857.
Iruela-Arispe M.L. and Davis G.E. (2009). Cellular and molecular
Kreuger J. and Phillipson M. (2016). Targeting vascular and leukocyte
mechanisms of vascular lumen formation. Dev. Cell 16, 222-231.
communication in angiogenesis, inflammation and fibrosis. Nat. Rev.
Jakobsson L., Franco C.A., Bentley K., Collins R.T., Ponsioen B.,
Drug Discov. 15, 125-142.
Aspalter I.M., Rosewell I., Busse M., Thurston G., Medvinsky A.,
Krishna Priya S., Nagare R.P., Sneha V.S., Sidhanth C., Bindhya S.,
Schulte-Merker S. and Gerhardt H. (2010). Endothelial cells
Manasa P. and Ganesan T.S. (2016). Tumour angiogenesis-Origin
dynamically compete for the tip cell position during angiogenic
of blood vessels. Int. J. Cancer 139, 729-735.
sprouting. Nat. Cell Biol. 12, 943-953.
Kugler A, Koelblinger P, Zelger B, Ahlgrimm-Siess V. and Laimer M.
Jin S.W. and Patterson C. (2009). The opening act: vasculogenesis and
(2016). Papillary intralymphatic angioendothelioma (PILA), also
the origins of circulation. Arterioscler. Thromb. Vasc. Biol. 29, 623-
referred to as Dabska tumour, in an 83-year-old woman. J. Eur.
629.
Acad. Dermatol. Venereol. 30, e59-e61.
Jin S.W., Beis D., Mitchell T., Chen J.N. and Stainier D.Y. (2005)
Kuo T., Sayers C.P. and Rosai J. (1976). Masson's "vegetant
Cellular and molecular analyses of vascular tube and lumen
intravascular hemangioendothelioma:" a lesion often mistaken for
formation in zebrafish. Development 132, 5199-5209.
angiosarcoma: study of seventeen cases located in the skin and soft
Kale S., Hanai J., Chan B., Karihaloo A., Grotendorst G., Cantley L. and
tissues. Cancer 38, 1227-1236.
Sukhatme V.P. (2005). Microarray analysis of in vitro pericyte
Kuo C.L, Chen P.C, Li W.Y. and Chu P.Y. (2015). Retiform
differentiation reveals an angiogenic program of gene expression.
hemangioendothelioma of the neck. J. Pathol. Transl. Med. 49, 171-
FASEB J. 19, 270-271.
173.
Kalka C., Masuda H., Takahashi T., Kalka-Moll W.M., Silver M.,
Kurz H., Gärtner T., Eggli P.S. and Christ B. (1996). First blood vessels
Kearney M., Li T., Isner J.M. and Asahara T. (2000). Transplantation
in the avian neural tube are formed by a combination of dorsal
of ex vivo expanded endothelial progenitor cells for therapeutic
angioblast immigration and ventral sprouting of endothelial cells.
neovascularization. Proc. Natl. Acad. Sci. USA 97, 3422-3427.
Dev. Biol. 173, 133-147.
Kanbe N., Kurosawa M., Nagata H., Yamashita T., Kurimoto F. and
Kurz H., Burri P.H. and Djonov V.G. (2003). Angiogenesis and vascular
Miyachi Y. (2000). Production of fibrogenic cytokines by cord blood-
remodeling by intussusception: from form to function. News Physiol.
derived cultured human mast cells. J. Allergy Clin. Immunol. 106,
Sci. 18, 65-70.
S85-S90.
Lamagna C. and Bergers G. (2006). The bone marrow constitutes a
Kandemir N.O., Narli Z.I., Kalayci M. and Ozdamar S.O. (2014). A rare
reservoir of pericyte progenitors. J. Leukoc. Biol. 80, 677-681.
pattern of angiogenesis in meningiomas: glomeruloid microvascular
Lange C., Ehlken C., Stahl A., Martin G., Hansen L. and Agostini H.T.
proliferation. Turk. Neurosurg. 24, 765-769.
(2009). Kinetics of retinal vaso-obliteration and neovascularisation in
Kashiwagi S., Izumi Y., Gohongi T., Demou Z.N., Xu L., Huang P.L.,
the oxygen-induced retinopathy (OIR) mouse model. Graefes Arch.
Buerk D.G., Munn L.L., Jain R.K. and Fukumura D. (2005). NO
Clin. Exp. Ophthalmol. 247, 1205-1211.
mediates mural cell recruitment and vessel morphogenesis in
Langlois S., Gingras D. and Béliveau R. (2004). Membrane type 1-
murine melanomas and tissue-engineered blood vessels. J. Clin.
matrix metalloproteinase (MT1-MMP) cooperates with sphingosine
Invest. 115, 1816-1827.
1-phosphate to induce endothelial cell migration and morphogenic
Kilarski W.W., Samolov B., Petersson L., Kvanta A. and Gerwins P.
differentiation. Blood 103, 3020-3028.
(2009). Biomechanical regulation of blood vessel growth during
Larrivée B., Niessen K., Pollet I., Corbel S.Y., Long M., Rossi F.M.,
tissue vascularization. Nat. Med. 15, 657-664.
Olive P.L. and Karsan A. (2005). Minimal contribution of marrow-
Kim E.S., Serur A., Huang J., Manley C.A., McCrudden K.W., Frischer
derived endothelial precursors to tumor vasculature. J Immunol.
J.S., Soffer S.Z., Ring L., New T., Zabski S., Rudge J.S., Holash J.,
175, 2890-2899.
Yancopoulos G.D., Kandel J.J. and Yamashiro D.J. (2002). Potent
le Noble F., Moyon D., Pardanaud L., Yuan L., Djonov V., Matthijsen R.,
VEGF blockade causes regression of coopted vessels in a model of
Bréant C., Fleury V. and Eichmann A. (2004). Flow regulates
neuroblastoma. Proc. Natl. Acad. Sci. USA 99, 11399-11404.
arterial-venous differentiation in the chick embryo yolk sac.
Kim H.K., Song K.S., Kim H.O., Chung J.H., Lee K.R., Lee Y.J., Lee
Development 131, 361-375.
12
Angiogenesis and related secondary
le Noble F., Fleury V., Pries A., Corvol P., Eichmann A. and Reneman
Lu X., Le Noble F., Yuan L., Jiang Q., De Lafarge B., Sugiyama D.,
R.S. (2005). Control of arterial branching morphogenesis in
Bréant C., Claes F., De Smet F., Thomas J.L., Autiero M., Carmeliet
embryogenesis: go with the flow. Cardiovasc. Res. 65, 619-628.
P., Tessier-Lavigne M. and Eichmann A. (2004). The netrin receptor
Leavesley D.I., Schwartz M.A., Rosenfeld M. and Cheresh D.A. (1993).
UNC5B mediates guidance events controlling morphogenesis of the
Integrin beta 1- and beta 3-mediated endothelial cell migration is
vascular system. Nature 432, 179-186.
triggered through distinct signalling mechanisms. J. Cell Biol. 121,
Lubarsky B. and Krasnow M.A. (2003). Tube morphogenesis: making
163-170.
and shaping biological tubes. Cell 112, 19-28.
Lee J.F., Ozaki H., Zhan X., Wang E., Hla T. and Lee M.J. (2006).
Macchiarelli G., Jiang J.Y., Nottola S.A. and Sato E. (2006).
Sphingosine-1-phosphate signaling regulates lamellipodia
Morphological patterns of angiogenesis in ovarian follicle capillary
localization of cortactin complexes in endothelial cells. Histochem.
networks. A scanning electron microscopy study of corrosion cast.
Cell Biol. 126, 297-304.
Microsc. Res. Tech. 69, 459-468.
Lee G.S., Filipovic N., Miele L.F., Lin M., Simpson D.C, Giney B.,
Maden C.H., Fantin A. and Ruhrberg C. (2009). Neuropilin ligands in
Konerding M.A., Tsuda A. and Mentzer S.J. (2010). Blood flow
vascular and neuronal patterning. Biochem. Soc. Trans. 37, 1228-
shapes intravascular pillar geometry in the chick chorioallantoic
1232.
membrane. J. Angiogenes. Res. 2, 11.
Madri J.A. and Stenn K.S. (1982). Aortic endothelial cell migration. l.
Lee G.S., Filipovic N., Lin M., Gibney B.C., Simpson D.C., Konerding
Matrix requirements and composition. Am. J. Pathol. 106, 180-1 86.
M.A., Tsuda A. and Mentzer S.J. (2011). Intravascular pillars and
Madri J.A. and Pratt B.M. (1986). Endothelial cell-matrix interactions: in
pruning in the extraembryonic vessels of chick embryos. Dev. Dyn.
vitro models of angiogenesis. J. Histochem. Cytochem. 34, 85-91.
240, 1335-1343.
Madrid J.F., Diaz-Flores L., Gutierrez R., Varela H., Valladares F.,
Lenard A., Ellertsdottir E., Herwig L., Krudewig A., Sauteur L., Belting
Rancel N. and Rodriguez F. (1998). Participation of angiogenesis
H.G. and Affolter M. (2013). In vivo analysis reveals a highly
from rat femoral veins in the neovascularization of adjacent
stereotypic morphogenetic pathway of vascular anastomosis. Dev.
occluded arteries. Histol. Histopathol 13, 1-11.
Cell 25, 492-506.
Lenard A., Daetwyler S., Betz C., Ellertsdottir E., Belting H.G., Huisken Makanya A.N., Stauffer D., Ribatti D., Burri P.H. and Djonov V. (2005).
Microvascular growth, development, and remodeling in the
J. and Affolter M. (2015). Endothelial cell self-fusion during vascular
embryonic avian kidney: the interplay between sprouting and
pruning. PLoS Biol. 13, e1002126.
Leslie J.D., Ariza-McNaughton L., Bermange A.L., McAdow R., Johnson intussusceptive angiogenic mechanisms. Microsc. Res. Tech. 66,
275-288.
S.L. and Lewis J. (2007). Endothelial signalling by the Notch ligand
Makanya A.N., Hlushchuk R., Baum O., Velinov N., Ochs M. and Djonov
Delta-like 4 restricts angiogenesis. Development 134, 839-844.
V. (2007). Microvascular endowment in the developing chicken
Li Q., Fukuda K., Lu Y., Nakamura Y., Chikama T., Kumagai N. and
embryo lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 292, L1136-
Nishida T. (2003). Enhancement by neutrophils of collagen
L1146.
degradation by corneal fibroblasts. J. Leukoc. Biol. 74, 412-419.
Makanya A.N., Hlushchuk R. and Djonov V.G. (2009). Intussusceptive
Li B., Li Y., Tian X.Y. and Li Z. (2013). Unusual multifocal intraosseous
angiogenesis and its role in vascular morphogenesis, patterning,
papillary intralymphatic angioendothelioma (Dabska tumor) of facial
and remodeling. Angiogenesis 12, 113-123.
bones: a case report and review of literature. Diagn. Pathol. 8, 160.
Makrilia N., Lappa T., Xyla V., Nikolaidis I. and Syrigos K. (2009). The
Liaw L. and Schwartz S.M. (1993). Microtubule disruption
role of angiogenesis in solid tumours: an overview. Eur. J. Intern.
stimulatesDNA synthesis in bovine endothelial cells and potentiates
Med. 20, 663-671.
cellular response to basic fibroblast growth factor. Am. J. Pathol.
Maltby S., Khazaie K. and McNagny K.M. (2009). Mast cells in tumor
143, 937-948.
growth: angiogenesis, tissue remodelling and immune-modulation.
Lin C.S. and Lue T.F. (2013). Defining vascular stem cells. Stem Cells
Biochim. Biophys. Acta 1796, 19-26.
Dev. 22, 1018-1026.
Manetti M., Guiducci S. and Matucci-Cerinic M. (2016). The crowded
Lin Y., Weisdorf D.J., Solovey A. and Hebbel R.P. (2000). Origins of
crossroad to angiogenesis in systemic sclerosis: where is the key to
circulating endothelial cells and endothelial outgrowth from blood. J.
the problem? Arthritis. Res. Ther. 18, 36.
Clin. Invest. 105, 71-77.
Maniotis A.J., Folberg R., Hess A., Seftor E.A., Gardner L.M., Pe'er J.,
Lin C.S., Xin Z.C., Deng C.H., Ning H., Lin G. and Lue T.F. (2010).
Trent J.M., Meltzer P.S. and Hendrix M.J. (1999). Vascular channel
Defining adipose tissue-derived stem cells in tissue and in culture.
formation by human melanoma cells in vivo and in vitro:
Histol. Histopathol. 25, 807-815.
vasculogenic mimicry. Am. J. Pathol. 155, 739-752.
Liu Q., Ouyang R., Chen P. and Zhou R. (2015). A case report of
Maquart F.X., Bellon G., Pasco S. and Monboisse J.C. (2004).
retiform hemangioendothelioma as pleural nodules with literature
Matrikines in the regulation of extracellular matrix degradation.
review. Diagn. Pathol. 10, 194.
Biochimie 87, 353-360.
Lobov I.B., Rao S., Carroll T.J., Vallance J.E., Ito M., Ondr J.K., Kurup
Matsuki M., Kabara M., Saito Y., Shimamura K., Minoshima A.,
S., Glass D.A., Patel M.S., Shu W., Morrisey E.E., McMahon A.P.,
Nishimura M., Aonuma T., Takehara N., Hasebe N. and Kawabe J.
Karsenty G. and Lang R.A. (2005). WNT7b mediates macrophage-
(2015). Ninjurin1 is a novel factor to regulate angiogenesis through
induced programmed cell death in patterning of the vasculature.
the function of pericytes. Circ. J. 79, 1363-1371.
Nature 437, 417-421.
Maumus M., Peyrafitte J.A., D'Angelo R., Fournier-Wirth C., Bouloumié
Lobov I.B., Renard R.A., Papadopoulos N., Gale N.W., Thurston G.,
A., Casteilla L., Sengenès C. and Bourin P. (2011). Native human
Yancopoulos G.D. and Wiegand S.J. (2007). Delta-like ligand 4
adipose stromal cells: localization, morphology and phenotype. Int.
(Dll4) is induced by VEGF as a negative regulator of angiogenic
J. Obes. (Lond) 35, 1141-1153.
sprouting. Proc. Natl. Acad. Sci. USA 104, 3219-3224.
Mazzone M., Dettori D., Leite de Oliveira R., Loges S., Schmidt T.,
12
Angiogenesis and related secondary
Jonckx B., Tian Y.M., Lanahan A.A., Pollard P., Ruiz de Almodovar
(2012). Stalk cell phenotype depends on integration of Notch and
C., De Smet F., Vinckier S., Aragonés J., Debackere K., Luttun A.,
Smad1/5 signaling cascades. Dev. Cell 22, 501-514.
Wyns S., Jordan B., Pisacane A., Gallez B., Lampugnani M.G.,
Mulligan-Kehoe M.J. and Simons M. (2008). Vascular disease in
Dejana E., Simons M, Ratcliffe P., Maxwell P. and Carmeliet P.
scleroderma: angiogenesis and vascular repair. Rheum. Dis. Clin.
(2009). Heterozygous deficiency of PHD2 restores tumor
North Am. 34, 73-79.
oxygenation and inhibits metastasis via endothelial normalization.
Myers K.A., Applegate K.T., Danuser G., Fischer R.S. and Waterman
Cell 136, 839-851.
C.M. (2011). Distinct ECM mechanosensing pathways regulate
McCracken J.S., Burger P.C. and Klintworth G.K. (1979). Morphologic
microtubule dynamics to control endothelial cell branching
observations on experimental comeal vascularization in the rat. Lab.
morphogenesis. J. Cell Biol. 192, 321-334.
Invest. 41, 519-530.
Nagy J.A., Brown L.F., Senger D.R., Lanir N., Van de Water L., Dvorak
McDonald D.M. and Choyke P.L. (2003). Imaging of angiogenesis: from
A.M. and Dvorak H.F. (1989). Pathogenesis of tumor stroma
microscope to clinic. Nat. Med. 9, 713-725.
generation: a critical role for leaky blood vessels and fibrin
Mehta D. and Malik A.B. (2006). Signaling mechanisms regulating
deposition. Biochim. Biophys. Acta 948, 305-326.
endothelial permeability. Physiol. Rev. 86, 279-367.
Nakayasu K. (1988). Origin of pericytes in neovascularization of rat
Mentzer S.J. and Konerding M.A. (2014). Intussusceptive angiogenesis:
cornea. Jpn. J. Ophthalmol. 32, 105-112.
expansion and remodeling of microvascular networks. Angiogenesis
Nehls V., Denzer K. and Drenckhahn D. (1992). Pericyte involvement in
17, 499-509.
capillary sprouting during angiogenesis in situ. Cell Tissue Res. 270,
Mihic-Probst D., Ikenberg K., Tinguely M., Schraml P., Behnke S.,
469-474.
Seifert B., Civenni G., Sommer L., Moch H. and Dummer R. (2012).
Neves R.I., Stevenson J., Hancey M.J., Vangelisti G., Miraliakbari R.,
Tumor cell plasticity and angiogenesis in human melanomas. PLoS
Mackay D. and Clarke L. (2011). Endovascular papillary
One 7, e33571.
angioendothelioma (Dabska tumor): underrecognized malignant
Miranville A., Heeschen C., Sengenès C., Curat C.A., Busse R. and
tumor in childhood. J. Pediatr. Surg. 46, e25-28.
Bouloumié A. (2004). Improvement of postnatal neovascularization
Nico B., Crivellato E., Guidolin D., Annese T., Longo V., Finato N.,
by human adipose tissue-derived stem cells. Circulation 110, 349-
Vacca A. and Ribatti D. (2010). Intussusceptive microvascular
355.
growth in human glioma. Clin. Exp. Med. 10, 93-98.
Moldovan L. and Moldovan N.I. (2005). Role of monocytes and
Nicosia R.F. and Madri J.A. (1987). The microvascular extracellular
macrophages in angiogenesis. EXS 94, 127-146.
matrix. Developmental changes during angiogenesis in the aortic
Moldovan N.I., Goldschmidt-Clermont P.J., Parker-Thornburg J.,
ring-plasma clot model. Am. J. Pathol. 128, 78-90.
Shapiro S.D. and Kolattukudy P.E. (2000). Contribution of
Nicosia R.F. and Villaschi S. (1995). Rat aortic smooth muscle cells
monocytes/macrophages to compensatory neovascularization: the
become pericytes during angiogenesis in vitro. Lab. Invest. 73, 658-
drilling of metalloelastase-positive tunnels in ischemic myocardium.
666.
Circ Res. 87, 378-384.
Ohki Y., Heissig B., Sato Y., Akiyama H., Zhu Z., Hicklin D.J., Shimada
Monboisse J.C., Oudart J.B., Ramont L., Brassart-Pasco S. and
K., Ogawa H., Daida H., Hattori K. and Ohsaka A. (2005).
Maquart F.X. (2014). Matrikines from basement membrane
Granulocyte colony-stimulating factor promotes neovascularization
collagens: a new anti-cancer strategy. Biochim. Biophys. Acta 1840,
by releasing vascular endothelial growth factor from neutrophils.
2589-2598.
FASEB J. 19, 2005-2007.
Moore M.A., Hattori K., Heissig B., Shieh J.H., Dias S., Crystal R.G. and
Ohtani H. (1992). Glomeruloid structures as vascular reaction in human
Rafii S. (2001). Mobilization of endothelial and hematopoietic stem
gastrointestinal carcinoma. Jpn. J. Cancer Res. 83, 1334-1340.
and progenitor cells by adenovector-mediated elevation of serum
Okada H., Tsuzuki T., Shindoh H., Nishigaki A., Yasuda K. and Kanzaki
levels of SDF-1, VEGF, and angiopoietin-1. Ann. NY Acad. Sci. 938,
H. (2014). Regulation of decidualization and angiogenesis in the
36-45.
human endometrium: mini review. J. Obstet. Gynaecol. Res. 40,
Moreau V., Tatin F., Varon C., Anies G., Savona-Baron C. and Génot E.
1180-1187.
(2006). Cdc42-driven podosome formation in endothelial cells. Eur.
Orlidge A. and D'Amore P.A. (1987). lnhibition of capillary endothelial
J. Cell Biol. 85, 319-325.
cell growth by pericytes and smooth muscle cells. J. Cell Biol. 105,
Morikawa S., Baluk P., Kaidoh T., Haskell A., Jain R. and McDonald D.
1455-1462.
(2002). Abnormalities in pericytes on blood vessels and endothelial
Osiak A.E., Zenner G. and Linder S. (2005). Subconfluent endothelial
sprouts in tumors. Am. J. Pathol. 160, 985-1000.
cells form podosomes downstream of cytokine and RhoGTPase
Moscatelli D. and Rifkin D.B. (1988). Membrane and matrix localization
signaling. Exp. Cell Res. 307, 342-353.
of proteinases: A common theme in tumor invasion and
Ozerdem U and Stallcup W.B. (2004). Pathological angiogenesis is
angiogenesis. Biochim. Biophys. Acta 948, 67-85.
reduced by targeting pericytes via the NG2 proteoglycan.
Moscatelli D., Gross J.L. and Rifkin D.B. (1981). Angiogenic factors
Angiogenesis 7, 269-276.
stimulate plasminogen activator and collagenase production
Ozerdem U., Grako K.A., Dahlin-Huppe K., Monosov E. and Stallcup
bycapillary endothelial cells. J. Cell Biol. 91, 201a
W.B. (2001). NG2 proteoglycan is expressed exclusively by mural
Mota A., Argenziano G., Zalaudek I., Piana S., Longo C., Moscarella E.
cells during vascular morphogenesis. Dev. Dyn. 222, 218-227.
and Lallas A. (2013). Clinical, dermoscopic and histopathologic
Paku S., Dezso K., Bugyik E., Tóvári J., Tímár J., Nagy P., Laszlo V.,
findings of retiform hemangioendothelioma. Dermatol. Pract.
Klepetko W. and Döme B. (2011). A new mechanism for pillar
Concept. 3, 11-14.
formation during tumor-induced intussusceptive angiogenesis:
Moya I.M., Umans L., Maas E., Pereira P.N., Beets K., Francis A., Sents
inverse sprouting. Am. J. Pathol. 179, 1573-1585.
W., Robertson E.J., Mummery C.L., Huylebroeck D. and Zwijsen A.
Patan S. (1998). TIE1 and TIE2 receptor tyrosine kinases inversely
12
Angiogenesis and related secondary
Tillet E., Vittet D., Féraud O., Moore R., Kemler R. and Huber P. (2005).
Wall R.T., Harker L.A., Quadracci L.J. and Striker G.E. (1978). Factors
N-cadherin deficiency impairs pericyte recruitment, and not
influencing endothelial cell proliferation in vitro. J. Cell Physiol. 96,
endothelial differentiation or sprouting, in embryonic stem cell-
203-213.
derived angiogenesis. Exp. Cell Res. 310, 392-400.
Walsh T.G., Metharom P. and Berndt M.C. (2015). The functional role of
Tirziu D., Jaba I.M., Yu P., Larrivée B., Coon B.G., Cristofaro B.,
platelets in the regulation of angiogenesis. Platelets 26, 199-211.
Zhuang Z.W., Lanahan A.A., Schwartz M.A., Eichmann A. and
Weavers H. and Skaer H. (2014). Tip cells: master regulators of
Simons M. (2012). Endothelial nuclear factor-κB-dependent
tubulogenesis? Semin. Cell Dev. Biol. 31, 91-99.
regulation of arteriogenesis and branching. Circulation 126, 2589-
Wesseling P., van der Laak J.A., de Leeuw H., Ruiter D.J. and Burger
2600.
P.C. (1994). Quantitative immunohistological analysis of the
Todorova D., Simoncini S., Lacroix R., Sabatier F. and Dignat-George
microvasculature in untreated human glioblastoma multiforme.
F. (2017). Extracellular vesicles in angiogenesis. Circ. Res. 120,
Computer-assisted image analysis of whole-tumor sections. J.
1658-1673.
Neurosurg. 81, 902-909.
Tsuda A., Turhan A., Konerding M., Ravnic D., Hanidziar D., Lin M. and
Wesseling P., Schlingemann R.O., Rietveld F.J., Link M., Burger P.C.
Mentzer S.J. (2009). Bimodal oscillation frequencies of blood flow in
and Ruiter D.J. (1995). Early and extensive contribution of
the inflammatory colon microcirculation. Anat. Rec. (Hoboken) 292,
pericytes/vascular smooth muscle cells to microvascular proliferation
65-72.
in glioblastoma multiforme: an immuno-light and immuno-electron
Tsuzuki H. and Sasa S. (1994). Ultrastructural observation of capillary
microscopic study. J. Neuropathol. Exp. Neurol. 54, 304-310.
sprouts in the dental organs of rat molars. Kaibogaku Zasshi 69,
Wietecha M.S., Cerny W.L. and DiPietro L.A. (2013). Mechanisms of
684-696.
vessel regression: toward an understanding of the resolution of
Tzima E., Kiosses W.B., del Pozo M.A. and Schwartz M.A. (2003).
angiogenesis. Curr. Top. Microbiol. Immunol. 367, 3-32.
Localized cdc42 activation, detected using a novel assay, mediates
Williams C.K., Li J.L., Murga M., Harris A.L. and Tosato G. (2006a). Up-
microtubule organizing center positioning in endothelial cells in
regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced
response to fluid shear stress. J. Biol. Chem. 278, 31020-
endothelial cell function. Blood 107, 931-939.
31023.
Williams J.L., Weichert A., Zakrzewicz A., Da Silva-Azevedo L., Pries
Tzima E., Irani-Tehrani M., Kiosses W.B., Dejana E., Schultz D.A.,
A.R., Baum O. and Egginton S. (2006b). Differential gene and
Engelhardt B., Cao G., DeLisser H. and Schwartz M.A. (2005). A
protein expression in abluminal sprouting and intraluminal splitting
mechanosensory complex that mediates the endothelial cell
forms of angiogenesis. Clin. Sci. (Lond) 110, 587-595.
response to fluid shear stress. Nature 437, 426-431.
Woad K.J. and Robinson R.S. (2016). Luteal angiogenesis and its
Udan R.S., Vadakkan T.J. and Dickinson M.E. (2013). Dynamic
control. Theriogenology 86, 221-228.
responses of endothelial cells to changes in blood flow during
Yana I., Sagara H., Takaki S., Takatsu K., Nakamura K., Nakao K.,
vascular remodeling of the mouse yolk sac. Development 140,
Katsuki M., Taniguchi S., Aoki T., Sato H., Weiss S.J. and Seiki M.
4041-4050.
(2007). Crosstalk between neovessels and mural cells directs the
Vajkoczy P., Blum S., Lamparter M., Mailhammer R., Erber R.,
site-specific expression of MT1-MMP to endothelial tip cells. J. Cell
Engelhardt B., Vestweber D. and Hatzopoulos A.K. (2003). Multistep
Sci. 120, 1607-1614.
nature of microvascular recruitment of ex vivo-expanded embryonic
Yu J.A., Castranova D., Pham V.N. and Weinstein B.M. (2015). Single-
endothelial progenitor cells during tumor angiogenesis. J. Exp. Med.
cell analysis of endothelial morphogenesis in vivo. Development
197, 1755-1765.
142, 2951-2961.
van Hinsbergh V.W. and Koolwijk P. (2008). Endothelial sprouting and
Yuri T., Yamazaki F., Takasu K., Shikata N. and Tsubura A. (2008).
angiogenesis: matrix metalloproteinases in the lead. Cardiovasc.
Glomeruloid hemangioma. Pathol. Int. 58, 390-395.
Res. 78, 203-212.
Zeng G., Taylor S.M., McColm J.R., Kappas N.C., Kearney J.B.,
Van Steenkiste C., Trachet B., Casteleyn C., van Loo D., Van
Williams L.H., Hartnett M.E. and Bautch V.L. (2007). Orientation of
Hoorebeke L., Segers P., Geerts A., Van Vlierberghe H. and Colle I.
endothelial cell division is regulated by VEGFsignaling during blood
(2010). Vascular corrosion casting: analyzing wall shear stress in
vessel formation. Blood 109, 1345-1352.
the portal vein and vascular abnormalities in portal hypertensive and
Zengin E., Chalajour F., Gehling U.M., Ito W.D., Treede H., Lauke H.,
cirrhotic rodents. Lab. Invest. 90, 1558-1572.
Weil J., Reichenspurner H., Kilic N. and Ergün S. (2006). Vascular
VanKlompenberg M.K., Manjarín R., Donovan C.E., Trott J.F. and
wall resident progenitor cells: asource for postnatal vasculogenesis.
Hovey R.C. (2016). Regulation and localization of vascular
Development 133, 1543-1551.
endothelial growth factor within the mammary glands during the
Zhang L., Yang N., Park J.W., Katsaros D., Fracchioli S., Cao G.,
transition from late gestation to lactation. Domest. Anim. Endocrinol.
O'Brien-Jenkins A., Randall T.C., Rubin S.C. and Coukos G. (2003).
54, 37-47.
Tumor-derived vascular endothelial growth factor up-regulates
Vitorino, P. and T. Meyer. (2008). Modular control of endothelial sheet
angiopoietin-2 in host endothelium and destabilizes host
migration. Genes Dev. 22, 3268-3281.
vasculature, supporting angiogenesis in ovarian cancer. Cancer
von Tell D., Armulik A. and Betsholtz C. (2006). Pericytes and vascular
Res. 63, 3403-3412.
stability. Exp. Cell Res. 312, 623-629.
Zhang S., Zhang D. and Sun B. (2007). Vasculogenic mimicry: current
Wacker A. and Gerhardt H. (2011). Endothelial development taking
status and future prospects. Cancer Lett. 254, 157-164.
shape. Curr. Opin. Cell Biol. 23, 676-685.
Zhang Y., Lin X., Dai Y., Hu X., Zhu H., Jiang Y. and Zhang S. (2016).
Wakui S. (1988). Two and three dimensional ultrastructural observation
Endometrial stem cells repair injured endometrium and induce
of two cell type angiogenesis in human granulation tissue. Virchows
angiogenesis via AKT and ERK pathways. Reproduction 152, 389-
Arch. (B) 56, 127-139.
402.
12
Angiogenesis and related secondary
Zheng Y., Chen X., Qian M., Zhang M., Zhang D., Bai C., Wang Q. and
Zhou A., Egginton S., Hudlická O. and Brown M.D. (1998). Internal
Wang X. (2014a). Human lung telocytes could promote the
division of capillaries in rat skeletal muscle in response to chronic
proliferation and angiogenesis of human pulmonary microvascular
vasodilator treatment with alpha1-antagonist prazosin. Cell Tissue
endothelial cells in vitro. Mol. Cell. Ther. 1, 2-3.
Res. 293, 293-303.
Zheng Y., Cretoiu D., Yan G., Cretoiu S.M., Popescu L.M., Fang H. and
Zhou Z., Apte S.S., Soininen R., Cao R., Baaklini G.Y., Rauser R.W.,
Wang X. (2014b). Protein profiling of human lung telocytes and
Wang J., Cao Y. and Tryggvason K. (2000). Impaired endochondral
microvascular endothelial cells using iTRAQ quantitative proteomics.
ossification and angiogenesis in mice deficient in membrane-type
J. Cell. Mol. Med. 18, 1035-1059.
matrix metalloproteinase I. Proc. Natl. Acad. Sci. USA 97, 4052-
Zheng Y., Cretoiu D., Yan G., Cretoiu S.M., Popescu L.M. and Wang X.
4057.
(2014c). Comparative proteomic analysis of human lung telocytes
with fibroblasts. J. Cell. Mol. Med. 18, 568-589.
Accepted July 19, 2017