Abstract
Tumor angiogenesis, the process by which blood vessels penetrate and grow in the tumor microenvironment, is essential for oxygen and nutrient supply and hence constitutes a key player for the survival of solid neoplasms. Different mechanisms of angiogenesis are developed during tumor progression such as vasculogenesis, sprouting angiogenesis, intussusception, and vasculogenic mimicry. The transition from a quiescent vasculature to an actively growing one follows a series of synchronic events and is finely tuned by a wide array of molecules and positive and negative regulators of angiogenesis. Beginning with blood vessel sprouting and endothelial cell proliferation, followed by vessel navigation, remodeling, stabilization, and maturation, and finishing with blood vessel regression, the main molecular factors involved in the progression of each step are profoundly detailed. When the balance between positive and negative regulators of angiogenesis is shifted toward proangiogenic molecules, the quiescent vasculature becomes activated and initiates the angiogenic state of tumor development. The role of intratumoral hypoxia as a potent activator of the angiogenic switch, its regulation, and a detailed description of normal and aberrant tumor vessels are also provided. The understanding of the foundations of these mechanisms is crucial for an effective therapeutic targeting of the angiogenic process.
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References
Adams RH, Eichmann A (2010) Axon guidance molecules in vascular patterning. Cold Spring Harb Perspect Biol 2(5):a001875. https://doi.org/10.1101/cshperspect.a001875. [pii] cshperspect.a001875
Akhurst RJ (2006) A sweet link between TGFbeta and vascular disease? Nat Genet 38(4):400–401. https://doi.org/10.1038/ng0406-400. [pii] ng0406-400
Andrae J, Gallini R, Betsholtz C (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22(10):1276–1312. https://doi.org/10.1101/gad.1653708
Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala SM, Baek KH, Rosenzweig A, Spiegelman BM (2008) HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 451(7181):1008–1012. https://doi.org/10.1038/nature06613. [pii] nature06613
Armstrong LC, Bornstein P (2003) Thrombospondins 1 and 2 function as inhibitors of angiogenesis. Matrix Biol 22(1):63–71. [pii] S0945053X03000052
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967
Augustin HG, Koh GY, Thurston G, Alitalo K (2009) Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 10(3):165–177. https://doi.org/10.1038/nrm2639. [pii] nrm2639
Autiero M, Waltenberger J, Communi D, Kranz A, Moons L, Lambrechts D, Kroll J, Plaisance S, De Mol M, Bono F, Kliche S, Fellbrich G, Ballmer-Hofer K, Maglione D, Mayr-Beyrle U, Dewerchin M, Dombrowski S, Stanimirovic D, Van Hummelen P, Dehio C, Hicklin DJ, Persico G, Herbert JM, Shibuya M, Collen D, Conway EM, Carmeliet P (2003) Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nat Med 9(7):936–943. https://doi.org/10.1038/nm884. [pii] nm884
Baluk P, Hashizume H, McDonald DM (2005) Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 15(1):102–111. https://doi.org/10.1016/j.gde.2004.12.005. [pii] S0959-437X(04)00191-1
Barallobre MJ, Pascual M, Del Rio JA, Soriano E (2005) The Netrin family of guidance factors: emphasis on Netrin-1 signalling. Brain Res Brain Res Rev 49(1):22–47. https://doi.org/10.1016/j.brainresrev.2004.11.003. [pii] S0165-0173(04)00176-6
Basile JR, Barac A, Zhu T, Guan KL, Gutkind JS (2004) Class IV semaphorins promote angiogenesis by stimulating Rho-initiated pathways through plexin-B. Cancer Res 64(15):5212–5224. https://doi.org/10.1158/0008–5472.CAN-04-0126. [pii] 64/15/5212
Bautch VL (2009) Endothelial cells form a phalanx to block tumor metastasis. Cell 136(5):810–812. https://doi.org/10.1016/j.cell.2009.02.021. [pii] S0092–8674(09)00197–4
Beenken A, Mohammadi M (2009) The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov 8(3):235–253. https://doi.org/10.1038/nrd2792. [pii] nrd2792
Benedito R, Roca C, Sorensen I, Adams S, Gossler A, Fruttiger M, Adams RH (2009) The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell 137(6):1124–1135. https://doi.org/10.1016/j.cell.2009.03.025. [pii] S0092–8674(09)00324–9
Benezra R, Rafii S, Lyden D (2001) The id proteins and angiogenesis. Oncogene 20(58):8334–8341. https://doi.org/10.1038/sj.onc.1205160
Bentley K, Mariggi G, Gerhardt H, Bates PA (2009) Tipping the balance: robustness of tip cell selection, migration and fusion in angiogenesis. PLoS Comput Biol 5(10):e1000549. https://doi.org/10.1371/journal.pcbi.1000549
Bertolini F, Paul S, Mancuso P, Monestiroli S, Gobbi A, Shaked Y, Kerbel RS (2003) Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 63(15):4342–4346. https://doi.org/10.1002/bies.1069
Bielenberg DR, Pettaway CA, Takashima S, Klagsbrun M (2006) Neuropilins in neoplasms: expression, regulation, and function. Exp Cell Res 312(5):584–593. https://doi.org/10.1016/j.yexcr.2005.11.024. [pii] S0014-4827(05)00555-0
Bloch W, Huggel K, Sasaki T, Grose R, Bugnon P, Addicks K, Timpl R, Werner S (2000) The angiogenesis inhibitor endostatin impairs blood vessel maturation during wound healing. FASEB J 14(15):2373–2376. https://doi.org/10.1096/fj.00-0490fje. [pii] 00-0490fje
Blouw B, Song H, Tihan T, Bosze J, Ferrara N, Gerber HP, Johnson RS, Bergers G (2003) The hypoxic response of tumors is dependent on their microenvironment. Cancer Cell 4(2):133–146. [pii] S1535610803001946
Bristow RG, Hill RP (2008) Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer 8(3):180–192. https://doi.org/10.1038/nrc2344. [pii] nrc2344
Burri PH, Hlushchuk R, Djonov V (2004) Intussusceptive angiogenesis: its emergence, its characteristics, and its significance. Dev Dyn 231(3):474–488. https://doi.org/10.1002/dvdy.20184
Caduff JH, Fischer LC, Burri PH (1986) Scanning electron microscope study of the developing microvasculature in the postnatal rat lung. Anat Rec 216(2):154–164. https://doi.org/10.1002/ar.1092160207
Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11(2):85–95. https://doi.org/10.1038/nrc2981. [pii] nrc2981
Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473(7347):298–307. https://doi.org/10.1038/nature10144. [pii] nature10144
Cavallaro U, Liebner S, Dejana E (2006) Endothelial cadherins and tumor angiogenesis. Exp Cell Res 312(5):659–667. https://doi.org/10.1016/j.yexcr.2005.09.019. [pii] S0014-4827(05)00455-6
Clark ER, Clark EL (1939) Microscopic observation on the growth of blood capillaries in the living mammal. Am J Anat 64:251–299
Corada M, Nyqvist D, Orsenigo F, Caprini A, Giampietro C, Taketo MM, Iruela-Arispe ML, Adams RH, Dejana E (2010) The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/notch signaling. Dev Cell 18(6):938–949. https://doi.org/10.1016/j.devcel.2010.05.006. [pii] S1534-5807(10)00214-5
De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M, Naldini L (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8(3):211–226. https://doi.org/10.1016/j.ccr.2005.08.002. [pii] S1535-6108(05)00260-6
Deb A, Skelding KA, Wang S, Reeder M, Simper D, Caplice NM (2004) Integrin profile and in vivo homing of human smooth muscle progenitor cells. Circulation 110(17):2673–2677. https://doi.org/10.1161/01.CIR.0000139842.15651.B2. [pii] 01.CIR.0000139842.15651.B2
Dejana E, Orsenigo F, Molendini C, Baluk P, McDonald DM (2009) Organization and signaling of endothelial cell-to-cell junctions in various regions of the blood and lymphatic vascular trees. Cell Tissue Res 335(1):17–25. https://doi.org/10.1007/s00441-008-0694-5
Desgrosellier JS, Cheresh DA (2009) Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 10(1):9–22. https://doi.org/10.1038/nrc2748. [pii] nrc2748
Dinney CP, Bielenberg DR, Perrotte P, Reich R, Eve BY, Bucana CD, Fidler IJ (1998) Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon-alpha administration. Cancer Res 58(4):808–814
DiSalvo J, Bayne ML, Conn G, Kwok PW, Trivedi PG, Soderman DD, Palisi TM, Sullivan KA, Thomas KA (1995) Purification and characterization of a naturally occurring vascular endothelial growth factor. Placenta growth factor heterodimer. J Biol Chem 270(13):7717–7723
Djonov V, Makanya AN (2005) New insights into intussusceptive angiogenesis. EXS 94:17–33
Dome F, Taziaux P, Boniver J, Fridman V, Delbecque K (2007) Ileum intussusception in an adult: a case report. Rev Med Liege 62(7–8):498–500
Du R, Lu KV, Petritsch C, Liu P, Ganss R, Passegue E, Song H, Vandenberg S, Johnson RS, Werb Z, Bergers G (2008) HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 13(3):206–220. https://doi.org/10.1016/j.ccr.2008.01.034. [pii] S1535-6108(08)00041-X
Duda DG, Kozin SV, Kirkpatrick ND, Xu L, Fukumura D, Jain RK (2011) CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies? Clin Cancer Res 17(8):2074–2080. https://doi.org/10.1158/1078–0432.CCR-10-2636. [pii] 1078–0432.CCR-10-2636
Eilken HM, Adams RH (2010) Dynamics of endothelial cell behavior in sprouting angiogenesis. Curr Opin Cell Biol 22(5):617–625
Fernando NT, Koch M, Rothrock C, Gollogly LK, D’Amore PA, Ryeom S, Yoon SS (2008) Tumor escape from endogenous, extracellular matrix-associated angiogenesis inhibitors by up-regulation of multiple proangiogenic factors. Clin Cancer Res 14(5):1529–1539. https://doi.org/10.1158/1078–0432.CCR-07-4126. [pii] 14/5/1529
Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676. https://doi.org/10.1038/nm0603-669. [pii] nm0603-669
Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82(1):4–6
Folkman J (2004) Endogenous angiogenesis inhibitors. APMIS 112(7–8):496–507. https://doi.org/10.1111/j.1600-0463.2004.apm11207-0809.x. [pii] APMapm11207-0809
Folkman J, Merler E, Abernathy C, Williams G (1971) Isolation of a tumor factor responsible for angiogenesis. J Exp Med 133(2):275–288
Fraisl P, Mazzone M, Schmidt T, Carmeliet P (2009) Regulation of angiogenesis by oxygen and metabolism. Dev Cell 16(2):167–179. https://doi.org/10.1016/j.devcel.2009.01.003. [pii] S1534-5807(09)00031-8
Frenkel S, Barzel I, Levy J, Lin AY, Bartsch DU, Majumdar D, Folberg R, Pe’er J (2008) Demonstrating circulation in vasculogenic mimicry patterns of uveal melanoma by confocal indocyanine green angiography. Eye (Lond) 22(7):948–952. https://doi.org/10.1038/sj.eye.6702783. [pii] 6702783
Gaengel K, Genove G, Armulik A, Betsholtz C (2009) Endothelial-mural cell signaling in vascular development and angiogenesis. Arterioscler Thromb Vasc Biol 29(5):630–638. https://doi.org/10.1161/ATVBAHA.107.161521. [pii] ATVBAHA.107.161521
Gale NW, Dominguez MG, Noguera I, Pan L, Hughes V, Valenzuela DM, Murphy AJ, Adams NC, Lin HC, Holash J, Thurston G, Yancopoulos GD (2004) Haploinsufficiency of delta-like 4 ligand results in embryonic lethality due to major defects in arterial and vascular development. Proc Natl Acad Sci USA 101(45):15949–15954. https://doi.org/10.1073/pnas.0407290101. [pii] 0407290101
Gerhardt H, Semb H (2008) Pericytes: gatekeepers in tumour cell metastasis? J Mol Med (Berl) 86(2):135–144. https://doi.org/10.1007/s00109-007-0258-2
Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161(6):1163–1177. https://doi.org/10.1083/jcb.200302047. [pii] jcb.200302047
Geudens I, Gerhardt H (2011) Coordinating cell behaviour during blood vessel formation. Development 138(21):4569–4583. https://doi.org/10.1242/dev.062323. [pii] dev.062323
Gluzman-Poltorak Z, Cohen T, Herzog Y, Neufeld G (2000) Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected]. J Biol Chem 275(24):18040–18045. https://doi.org/10.1074/jbc.M909259199. [pii] M909259199
Goede V, Schmidt T, Kimmina S, Kozian D, Augustin HG (1998) Analysis of blood vessel maturation processes during cyclic ovarian angiogenesis. Lab Investig 78(11):1385–1394
Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, Jain RK (2011) Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev 91(3):1071–1121. https://doi.org/10.1152/physrev.00038.2010. [pii] 91/3/1071
Gridley T (2010) Notch signaling in the vasculature. Curr Top Dev Biol 92:277–309. https://doi.org/10.1016/S0070-2153(10)92009-7. [pii] S0070-2153(10)92009-7
Gupta MK, Qin RY (2003) Mechanism and its regulation of tumor-induced angiogenesis. World J Gastroenterol 9(6):1144–1155
Guttmann-Raviv N, Kessler O, Shraga-Heled N, Lange T, Herzog Y, Neufeld G (2006) The neuropilins and their role in tumorigenesis and tumor progression. Cancer Lett 231(1):1–11. https://doi.org/10.1016/j.canlet.2004.12.047. [pii] S0304-3835(05)00005-4
Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86(3):353–364. [pii] S0092-8674(00)80108-7
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013. [pii] S0092-8674(11)00127-9
Hattori K, Dias S, Heissig B, Hackett NR, Lyden D, Tateno M, Hicklin DJ, Zhu Z, Witte L, Crystal RG, Moore MA, Rafii S (2001) Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 193(9):1005–1014
Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109(5):625–637. [pii] S0092867402007547
Hendrix MJ, Seftor EA, Hess AR, Seftor RE (2003) Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma. Nat Rev Cancer 3(6):411–421. https://doi.org/10.1038/nrc1092. [pii] nrc1092
Holmgren L, O’Reilly MS, Folkman J (1995) Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1(2):149–153
Iruela-Arispe ML, Davis GE (2009) Cellular and molecular mechanisms of vascular lumen formation. Dev Cell 16(2):222–231. https://doi.org/10.1016/j.devcel.2009.01.013. [pii] S1534-5807(09)00041-0
Iruela-Arispe ML, Dvorak HF (1997) Angiogenesis: a dynamic balance of stimulators and inhibitors. Thromb Haemost 78(1):672–677
Jaffe RB (2000) Importance of angiogenesis in reproductive physiology. Semin Perinatol 24(1):79–81
Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9(6):685–693. https://doi.org/10.1038/nm0603-685. [pii] nm0603-685
Jakobsson L, Franco CA, Bentley K, Collins RT, Ponsioen B, Aspalter IM, Rosewell I, Busse M, Thurston G, Medvinsky A, Schulte-Merker S, Gerhardt H (2010) Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat Cell Biol 12(10):943–953. https://doi.org/10.1038/ncb2103. [pii] ncb2103
Jin F, Brockmeier U, Otterbach F, Metzen E (2012) New insight into the SDF-1/CXCR4 axis in a breast carcinoma model: hypoxia-induced endothelial SDF-1 and tumor cell CXCR4 are required for tumor cell intravasation. Mol Cancer Res 10(8):1021–1031. https://doi.org/10.1158/1541–7786.MCR-11-0498. [pii] 1541–7786.MCR-11-0498
Jinnin M, Medici D, Park L, Limaye N, Liu Y, Boscolo E, Bischoff J, Vikkula M, Boye E, Olsen BR (2008) Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma. Nat Med 14(11):1236–1246. https://doi.org/10.1038/nm.1877. [pii] nm.1877
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438(7069):820–827. https://doi.org/10.1038/nature04186. [pii] nature04186
Kim J, Oh WJ, Gaiano N, Yoshida Y, Gu C (2011) Semaphorin 3E-Plexin-D1 signaling regulates VEGF function in developmental angiogenesis via a feedback mechanism. Genes Dev 25(13):1399–1411. https://doi.org/10.1101/gad.2042011. [pii] 25/13/1399
Kopp HG, Avecilla ST, Hooper AT, Rafii S (2005) The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology (Bethesda) 20:349–356. https://doi.org/10.1152/physiol.00025.2005. [pii] 20/5/349
Kopp HG, Hooper AT, Broekman MJ, Avecilla ST, Petit I, Luo M, Milde T, Ramos CA, Zhang F, Kopp T, Bornstein P, Jin DK, Marcus AJ, Rafii S (2006) Thrombospondins deployed by thrombopoietic cells determine angiogenic switch and extent of revascularization. J Clin Invest 116(12):3277–3291. https://doi.org/10.1172/JCI29314, https://doi.org/10.1158/0008-5472.CAN-07-2706
Lamouille S, Mallet C, Feige JJ, Bailly S (2002) Activin receptor-like kinase 1 is implicated in the maturation phase of angiogenesis. Blood 100(13):4495–4501. https://doi.org/10.1182/blood.V100.13.4495. [pii] 100/13/4495
LaRochelle WJ, May-Siroff M, Robbins KC, Aaronson SA (1991) A novel mechanism regulating growth factor association with the cell surface: identification of a PDGF retention domain. Genes Dev 5(7):1191–1199
Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, Ferrara N, Nagy A, Roos KP, Iruela-Arispe ML (2007) Autocrine VEGF signaling is required for vascular homeostasis. Cell 130(4):691–703. https://doi.org/10.1016/j.cell.2007.06.054. [pii] S0092-8674(07)00905-1
Leslie JD, Ariza-McNaughton L, Bermange AL, McAdow R, Johnson SL, Lewis J (2007) Endothelial signalling by the notch ligand Delta-like 4 restricts angiogenesis. Development 134(5):839–844. https://doi.org/10.1242/dev.003244. [pii] dev.003244
Li H, Fredriksson L, Li X, Eriksson U (2003) PDGF-D is a potent transforming and angiogenic growth factor. Oncogene 22(10):1501–1510. https://doi.org/10.1038/sj.onc.1206223. [pii] 1206223
London NR, Smith MC, Li DY (2009) Emerging mechanisms of vascular stabilization. J Thromb Haemost 7(Suppl 1):57–60. https://doi.org/10.1111/j.1538-7836.2009.03421.x. [pii] JTH3421
Lu X, Le Noble F, Yuan L, Jiang Q, De Lafarge B, Sugiyama D, Breant C, Claes F, De Smet F, Thomas JL, Autiero M, Carmeliet P, Tessier-Lavigne M, Eichmann A (2004) The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 432(7014):179–186. https://doi.org/10.1038/nature03080. [pii] nature03080
Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F, Nagy JA, Hooper A, Priller J, De Klerck B, Compernolle V, Daci E, Bohlen P, Dewerchin M, Herbert JM, Fava R, Matthys P, Carmeliet G, Collen D, Dvorak HF, Hicklin DJ, Carmeliet P (2002) Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 8(8):831–840. https://doi.org/10.1038/nm731. [pii] nm731
Ma Z, Qin H, Benveniste EN (2001) Transcriptional suppression of matrix metalloproteinase-9 gene expression by IFN-gamma and IFN-beta: critical role of STAT-1alpha. J Immunol 167(9):5150–5159
Maeshima Y, Sudhakar A, Lively JC, Ueki K, Kharbanda S, Kahn CR, Sonenberg N, Hynes RO, Kalluri R (2002) Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. Science 295(5552):140–143. https://doi.org/10.1126/science.1065298. [pii] 295/5552/140
Majmundar AJ, Wong WJ, Simon MC (2010) Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 40(2):294–309. https://doi.org/10.1016/j.molcel.2010.09.022. [pii] S1097-2765(10)00750-1
Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe'er J, Trent JM, Meltzer PS, Hendrix MJ (1999) Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol 155(3):739–752. https://doi.org/10.1016/S0002–9440(10)65173-5. [pii] S0002–9440(10)65173–5
Mazzone M, Dettori D, Leite de Oliveira R, Loges S, Schmidt T, Jonckx B, Tian YM, Lanahan AA, Pollard P, Ruiz de Almodovar C, De Smet F, Vinckier S, Aragones J, Debackere K, Luttun A, Wyns S, Jordan B, Pisacane A, Gallez B, Lampugnani MG, Dejana E, Simons M, Ratcliffe P, Maxwell P, Carmeliet P (2009) Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 136(5):839–851. https://doi.org/10.1016/j.cell.2009.01.020. [pii] S0092–8674(09)00068–3
Mezquita P, Parghi SS, Brandvold KA, Ruddell A (2005) Myc regulates VEGF production in B cells by stimulating initiation of VEGF mRNA translation. Oncogene 24(5):889–901. https://doi.org/10.1038/sj.onc.1208251. [pii] 1208251
Mosch B, Reissenweber B, Neuber C, Pietzsch J (2010) Eph receptors and ephrin ligands: important players in angiogenesis and tumor angiogenesis. J Oncol 2010:135285. https://doi.org/10.1155/2010/135285
Murakami M, Nguyen LT, Zhuang ZW, Moodie KL, Carmeliet P, Stan RV, Simons M (2008) The FGF system has a key role in regulating vascular integrity. J Clin Invest 118(10):3355–3366. https://doi.org/10.1172/JCI35298
Noh YH, Matsuda K, Hong YK, Kunstfeld R, Riccardi L, Koch M, Oura H, Dadras SS, Streit M, Detmar M (2003) An N-terminal 80 kDa recombinant fragment of human thrombospondin-2 inhibits vascular endothelial growth factor induced endothelial cell migration in vitro and tumor growth and angiogenesis in vivo. J Invest Dermatol 121(6):1536–1543. https://doi.org/10.1046/j.1523-1747.2003.12643.x. [pii] S0022-202X(15)30563-7
Page EL, Chan DA, Giaccia AJ, Levine M, Richard DE (2008) Hypoxia-inducible factor-1alpha stabilization in nonhypoxic conditions: role of oxidation and intracellular ascorbate depletion. Mol Biol Cell 19(1):86–94. https://doi.org/10.1091/mbc.E07-06-0612. [pii] E07-06-0612
Paku S, Paweletz N (1991) First steps of tumor-related angiogenesis. Lab Investig 65(3):334–346
Pardali E, Goumans MJ, ten Dijke P (2010) Signaling by members of the TGF-beta family in vascular morphogenesis and disease. Trends Cell Biol 20(9):556–567. https://doi.org/10.1016/j.tcb.2010.06.006. [pii] S0962-8924(10)00121-2
Park KW, Morrison CM, Sorensen LK, Jones CA, Rao Y, Chien CB, Wu JY, Urness LD, Li DY (2003) Robo4 is a vascular-specific receptor that inhibits endothelial migration. Dev Biol 261(1):251–267. [pii] S0012160603002586
Presta M, Dell'Era P, Mitola S, Moroni E, Ronca R, Rusnati M (2005) Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 16(2):159–178. https://doi.org/10.1016/j.cytogfr.2005.01.004. [pii] S1359-6101(05)00005-5
Quaegebeur A, Segura I, Carmeliet P (2010) Pericytes: blood-brain barrier safeguards against neurodegeneration? Neuron 68(3):321–323. https://doi.org/10.1016/j.neuron.2010.10.024. [pii] S0896–6273(10)00874–3
Reynolds LP, Grazul-Bilska AT, Redmer DA (2000) Angiogenesis in the corpus luteum. Endocrine 12(1):1–9. https://doi.org/10.1385/ENDO:12:1:1. [pii] ENDO:12:1:1
Ribatti D (2009) Endogenous inhibitors of angiogenesis: a historical review. Leuk Res 33(5):638–644. https://doi.org/10.1016/j.leukres.2008.11.019. [pii] S0145-2126(08)00507-9
Ribatti D, Nico B, Floris C, Mangieri D, Piras F, Ennas MG, Vacca A, Sirigu P (2005) Microvascular density, vascular endothelial growth factor immunoreactivity in tumor cells, vessel diameter and intussusceptive microvascular growth in primary melanoma. Oncol Rep 14(1):81–84
Roca C, Adams RH (2007) Regulation of vascular morphogenesis by notch signaling. Genes Dev 21(20):2511–2524. https://doi.org/10.1101/gad.1589207. [pii] 21/20/2511
Roskoski R Jr (2008) VEGF receptor protein-tyrosine kinases: structure and regulation. Biochem Biophys Res Commun 375(3):287–291. https://doi.org/10.1016/j.bbrc.2008.07.121. [pii] S0006-291X(08)01350-8
Roukens MG, Alloul-Ramdhani M, Baan B, Kobayashi K, Peterson-Maduro J, van Dam H, Schulte-Merker S, Baker DA (2010) Control of endothelial sprouting by a Tel-CtBP complex. Nat Cell Biol 12(10):933–942. https://doi.org/10.1038/ncb2096. [pii] ncb2096
Saharinen P, Eklund L, Miettinen J, Wirkkala R, Anisimov A, Winderlich M, Nottebaum A, Vestweber D, Deutsch U, Koh GY, Olsen BR, Alitalo K (2008) Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nat Cell Biol 10(5):527–537. https://doi.org/10.1038/ncb1715. [pii] ncb1715
Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu ME, Acker T, Acker-Palmer A (2010) Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 465(7297):487–491. https://doi.org/10.1038/nature08995. [pii] nature08995
Schwartz JD, Rowinsky EK, Youssoufian H, Pytowski B, Wu Y (2010) Vascular endothelial growth factor receptor-1 in human cancer: concise review and rationale for development of IMC-18F1 (human antibody targeting vascular endothelial growth factor receptor-1). Cancer 116(4 Suppl):1027–1032. https://doi.org/10.1002/cncr.24789
Seftor EA, Brown KM, Chin L, Kirschmann DA, Wheaton WW, Protopopov A, Feng B, Balagurunathan Y, Trent JM, Nickoloff BJ, Seftor RE, Hendrix MJ (2005) Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma microenvironment. Cancer Res 65(22):10164–10169. https://doi.org/10.1158/0008–5472.CAN-05-2497. [pii] 65/22/10164
Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3(10):721–732. https://doi.org/10.1038/nrc1187. [pii] nrc1187
Serini G, Valdembri D, Zanivan S, Morterra G, Burkhardt C, Caccavari F, Zammataro L, Primo L, Tamagnone L, Logan M, Tessier-Lavigne M, Taniguchi M, Puschel AW, Bussolino F (2003) Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature 424(6947):391–397. https://doi.org/10.1038/nature01784. [pii] nature01784
St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW (2000) Genes expressed in human tumor endothelium. Science 289(5482):1197–1202. [pii] 8729
Stockmann C, Doedens A, Weidemann A, Zhang N, Takeda N, Greenberg JI, Cheresh DA, Johnson RS (2008) Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature 456(7223):814–818. https://doi.org/10.1038/nature07445. [pii] nature07445
Stratman AN, Davis GE (2011) Endothelial cell-pericyte interactions stimulate basement membrane matrix assembly: influence on vascular tube remodeling, maturation, and stabilization. Microsc Microanal 18(1):68–80. https://doi.org/10.1017/S1431927611012402. [pii] S1431927611012402
Suchting S, Bicknell R, Eichmann A (2006) Neuronal clues to vascular guidance. Exp Cell Res 312(5):668–675. https://doi.org/10.1016/j.yexcr.2005.11.009. [pii] S0014-4827(05)00531-8
Sudhakar A, Nyberg P, Keshamouni VG, Mannam AP, Li J, Sugimoto H, Cosgrove D, Kalluri R (2005) Human alpha1 type IV collagen NC1 domain exhibits distinct antiangiogenic activity mediated by alpha1beta1 integrin. J Clin Invest 115(10):2801–2810. https://doi.org/10.1172/JCI24813
Sun B, Zhang S, Zhao X, Zhang W, Hao X (2004) Vasculogenic mimicry is associated with poor survival in patients with mesothelial sarcomas and alveolar rhabdomyosarcomas. Int J Oncol 25(6):1609–1614
Taylor LM, Khachigian LM (2000) Induction of platelet-derived growth factor B-chain expression by transforming growth factor-beta involves transactivation by Smads. J Biol Chem 275(22):16709–16716. [pii] 275/22/16709
Thurston G, Noguera-Troise I, Yancopoulos GD (2007) The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth. Nat Rev Cancer 7(5):327–331. https://doi.org/10.1038/nrc2130. [pii] nrc2130
Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95(4):343–353. https://doi.org/10.1161/01.RES.0000137877.89448.78. [pii] 95/4/343
Vaupel P (2004) The role of hypoxia-induced factors in tumor progression. Oncologist 9(Suppl 5):10–17. https://doi.org/10.1634/theoncologist.9-90005-10. [pii] 9/suppl_ 5/10
Vinals F, Pouyssegur J (2001) Transforming growth factor beta1 (TGF-beta1) promotes endothelial cell survival during in vitro angiogenesis via an autocrine mechanism implicating TGF-alpha signaling. Mol Cell Biol 21(21):7218–7230. https://doi.org/10.1128/MCB.21.21.7218-7230.2001
Volpert OV, Alani RM (2003) Wiring the angiogenic switch: Ras, Myc, and Thrombospondin-1. Cancer Cell 3(3):199–200. [pii] S1535610803000564
Wang B, Xiao Y, Ding BB, Zhang N, Yuan X, Gui L, Qian KX, Duan S, Chen Z, Rao Y, Geng JG (2003) Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. Cancer Cell 4(1):19–29. [pii] S1535610803001648
Warren CM, Iruela-Arispe ML (2010) Signaling circuitry in vascular morphogenesis. Curr Opin Hematol 17(3):213–218. https://doi.org/10.1097/MOH.0b013e32833865d1
Wilson BD, Ii M, Park KW, Suli A, Sorensen LK, Larrieu-Lahargue F, Urness LD, Suh W, Asai J, Kock GA, Thorne T, Silver M, Thomas KR, Chien CB, Losordo DW, Li DY (2006) Netrins promote developmental and therapeutic angiogenesis. Science 313(5787):640–644. https://doi.org/10.1126/science.1124704. [pii] 1124704
Yan M, Callahan CA, Beyer JC, Allamneni KP, Zhang G, Ridgway JB, Niessen K, Plowman GD (2010) Chronic DLL4 blockade induces vascular neoplasms. Nature 463(7282):E6–E7. https://doi.org/10.1038/nature08751. [pii] nature08751
Yang SL, Liu LP, Jiang JX, Xiong ZF, He QJ, Wu C (2014) The correlation of expression levels of HIF-1alpha and HIF-2alpha in hepatocellular carcinoma with capsular invasion, portal vein tumor thrombi and patients’ clinical outcome. Jpn J Clin Oncol 44(2):159–167. https://doi.org/10.1093/jjco/hyt194. [pii] hyt194
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Zuazo-Gaztelu, I., Casanovas, O. (2019). Mechanisms of Tumor Angiogenesis. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-33673-2_1
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