Positive and negative modulation of angiogenesis by VEGFR1 ligands

Science Signaling

Volumn 2, Issue 59, 2009, Pages

  Cao, Yihai ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

PLACENTAL GROWTH FACTOR; VASCULOTROPIN; VASCULOTROPIN A; VASCULOTROPIN B; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3; ANGIOGENESIS MODULATOR; LIGAND; MEMBRANE PROTEIN; PIGF PROTEIN, HUMAN;

ANGIOGENESIS; BLOOD VESSEL PERMEABILITY; CANCER THERAPY; CARCINOGENESIS; LYMPHANGIOGENESIS; METASTASIS; PRIORITY JOURNAL; REVIEW; TUMOR GROWTH; ALTERNATIVE RNA SPLICING; BIOLOGICAL MODEL; GENETICS; METABOLISM; NEOPLASM; NEOVASCULARIZATION (PATHOLOGY); PATHOPHYSIOLOGY; PHYSIOLOGY;

ALTERNATIVE SPLICING; ANGIOGENESIS MODULATING AGENTS; LIGANDS; MEMBRANE PROTEINS; MODELS, BIOLOGICAL; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; NEOVASCULARIZATION, PHYSIOLOGIC; VASCULAR ENDOTHELIAL GROWTH FACTOR B; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1;

EID: 66149086950     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.259re1     Document Type: Review

References (132)

1. H. F. Dvorak, M. Detmar, K. P. Claffey, J. A. Nagy, L. van de Water, D. R. Senger, Vascular permeability factor/vascular endothelial growth factor: An important mediator of angiogenesis in malignancy and inflammation. Int. Arch. Allergy Immunol.107, 233-235 (1995).
2. M. A. Björndahl, R. Cao, J. B. Burton, E. Brak-enhielm, P. Religa, D. Galter, L. Wu, Y. Cao, Vascular endothelial growth factor-A promotes peritumoral lymphangiogenesis and lymphatic metastasis. Cancer Res. 65, 9261-9268 (2005). (Pubitemid 41507992)
3. L. M. Ellis, D. J. Hicklin, VEGF-targeted therapy: Mechanisms of anti-tumour activity. Nat. Rev. Cancer8, 579-591 (2008).
4. N. Ferrara, VEGF as a therapeutic target in cancer. Oncology69 (suppl. 3), 11-16 (2005). (Pubitemid 41680948)
5. P. Carmeliet, R. K. Jain, Angiogenesis in cancer and other diseases. Nature 407, 249-257 (2000).
6. H. Hurwitz, L. Fehrenbacher, W. Novotny, T. Cartwright, J. Hainsworth, W. Heim, J. Berlin, A. Baron, S. Griffing, E. Holmgren, N. Ferrara, G. Fyfe, B. Rogers, R. Ross, F. Kabbinavar, Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med.350, 2335-2342 (2004). (Pubitemid 38702844)
7. A. Sandler, R. Gray, M. C. Perry, J. Brahmer, J. H. Schiller, A. Dowlati, R. Lilenbaum, D. H. Johnson, Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med.355, 2542-2550 (2006). (Pubitemid 44917502)
8. B. Escudier, A. Pluzanska, P. Koralewski, A. Ravaud, S. Bracarda, C. Szczylik, C. B. Escudier, A. Pluzanska, P. Koralewski, A. Ravaud, S. Bracarda,C. Szczylik, Chevreau, M. Filipek, B. Melichar, E. Bajetta, V. Gorbunova, J. O. Bay, I. Bodrogi, A. Jagiel-lo-Gruszfeld, N. Moore, Bevacizumab plus in-terferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomised, double-blind phase III trial. Lancet 370, 2103-2111 (2007). (Pubitemid 350296300)
9. K. Miller, M. Wang, J. Gralow, M. Dickler, M. Cobleigh, E. A. Perez, T. Shenkier, D. Cella, N. E. Davidson, Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N. Engl. J. Med. 357, 2666-2676 (2007).
10. E. M. Stone, A very effective treatment for neovascular macular degeneration. N. Engl. J. Med.355, 1493-1495 (2006). (Pubitemid 44511565)
11. R. S. Kerbel, Tumor angiogenesis. N. Engl. J. Med.358, 2039-2049 (2008).
12. C. Booth, Bevacizumab in advanced colorec-tal cancer: A challenge to the current paradigm. J. Clin. Oncol. 26, 4693-4695 (2008).
13. G. Bergers, D. Hanahan, Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer8, 592-603 (2008).
14. Y. Crawford, I. Kasman, L. Yu, C. Zhong, X. Wu, Z. Modrusan, J. Kaminker, N. Ferrara, PDGF-C mediates the angiogenic and tumori-genic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell15, 21-34 (2009).
15. Y. Cao, R. Cao, E. M. Hedlund, R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways. J. Mol. Med. 86, 785-789 (2008).
16. Y. Shaked, A. Ciarrocchi, M. Franco, C. R. Lee, S. Man, A. M. Cheung, D. J. Hicklin, D. Chaplin, F. S. Foster, R. Benezra, R. S. Kerbel, Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors. Science313, 1785-1787 (2006). (Pubitemid 44454154)
17. M. Orlandini, L. Marconcini, R. Ferruzzi, S. Oliviero, Identification of a c-fos-induced gene that is related to the platelet-derived growth factor/vascular endothelial growth factor family. Proc. Natl. Acad. Sci. U.S.A.93, 11675-11680 (1996). (Pubitemid 26347181)
18. D. Maglione, V. Guerriero, G. Viglietto, P. Delli-Bovi, M. G. Persico, Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc. Natl. Acad. Sci. U.S.A.88, 9267-9271 (1991). (Pubitemid 21915612)
19. B. Olofsson, K. Pajusola, A. Kaipainen, G. von Euler, V. Joukov, O. Saksela, A. Orpana, R. F. Pettersson, K. Alitalo, U. Eriksson, Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc. Natl. Acad. Sci. U.S.A.93, 2576-2581 (1996). (Pubitemid 26104389)
20. V. Joukov, K. Pajusola, A. Kaipainen, D. Chilov, I. Lahtinen, E. Kukk, O. Saksela, N. Kalkkinen, K. Alitalo, A novel vascular endo-thelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 15, 290-298 (1996). (Pubitemid 26029207)
21. Y. Cao, W. R. Ji, P. Qi, A. Rosin, Y. Cao, Placenta growth factor: Identification and characterization of a novel isoform generated by RNA alternative splicing. Biochem. Biophys. Res.Commun.235, 493-498 (1997). (Pubitemid 27326507)
22. M. Caunt, J. Mak, W. C. Liang, S. Stawicki, Q. Pan, R. K. Tong, J. Kowalski, C. Ho, H. B. Reslan, J. Ross, L. Berry, I. Kasman, C. Zlot, Z. Cheng, J. Le Couter, E. H. Filvaroff, G. Plowman, F. Peale, D. French, R. Carano, A. W. Koch, Y. Wu, R. J. Watts, M. Tessier-Lavi-gne, A. Bagri, Blocking neuropilin-2 function inhibits tumor cell metastasis. Cancer Cell13, 331-342 (2008). (Pubitemid 351446192)
23. T. Makinen, B. Olofsson, T. Karpanen, U. Hell-man, S. Soker, M. Klagsbrun, U. Eriksson, K. Alitalo, Differential binding of vascular en-dothelial growth factor B splice and proteolytic isoforms to neuropilin-1. J. Biol. Chem. 274, 21217-21222 (1999). (Pubitemid 129519630)
24. R. Mamluk, Z. Gechtman, M. E. Kutcher, N. Gasiunas, J. Gallagher, M. Klagsbrun, Neuro-pilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain. J. Biol. Chem. 277, 24818-24825 (2002). (Pubitemid 34952014)
25. M. Migdal, B. Huppertz, S. Tessler, A. Comfor-ti, M. Shibuya, R. Reich, H. Baumann, G. Neufeld, Neuropilin-1 is a placenta growth factor-2 receptor. J. Biol. Chem. 273, 22272-22278 (1998). (Pubitemid 28399784)
26. G. Neufeld, O. Kessler, Y. Herzog, The interaction of neuropilin-1 and neuropilin-2 with ty-rosine-kinase receptors for VEGF. Adv. Exp. Med. Biol.515, 81-90 (2002). (Pubitemid 36324184)
27. S. Soker, S. Takashima, H. Q. Miao, G. Neufeld, M. Klagsbrun, Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothe-lial growth factor. Cell92, 735-745 (1998). (Pubitemid 28155313)
28. Y. Cao, P. Linden, J. Farnebo, R. Cao, A. Eriksson, V. Kumar, J. H. Qi, L. Claesson-Welsh, K. Alitalo, Vascular endothelial growth factor C induces angiogenesis in vivo. Proc. Natl. Acad. Sci. U.S.A.95, 14389-14394 (1998). (Pubitemid 28549377)
29. Y. Sato, S. Kanno, N. Oda, M. Abe, M. Ito, K. Shitara, M. Shibuya, Properties of two VEGF receptors, Flt-1 and KDR, in signal transduc-tion. Ann. N.Y. Acad. Sci. 902, 201-207 (2000). (Pubitemid 30389124)
30. M. Shibuya, VEGF-receptor inhibitors for anti-angiogenesis. Nippon Yakurigaku Zasshi 122, 498-503 (2003). (Pubitemid 38019942)
31. W. Yang, H. Ahn, M. Hinrichs, R. J. Torry, D. S. Torry, Evidence of a novel isoform of placenta growth factor (PlGF-4) expressed in human trophoblast and endothelial cells. J. Reprod. Immunol.60, 53-60 (2003). (Pubitemid 37272295)
32. D. Maglione, V. Guerriero, G. Viglietto, M. G. Ferraro, O. Aprelikova, K. Alitalo, S. Del Vec-chio, K. J. Lei, J. Y. Chou, M. G. Persico, Tw o alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14. Oncogene8, 925-931 (1993). (Pubitemid 23087424)
33. B. Olofsson, K. Pajusola, G. von Euler, D. Chilov, K. Alitalo, U. Eriksson, Genomic organization of the mouse and human genes for vascular endothelial growth factor B (VEGF-B) and characterization of a second splice isoform. J. Biol. Chem. 271, 19310-19317 (1996). (Pubitemid 26271600)
34. Y. Cao, H. Chen, L. Zhou, M. K. Chiang, B. Anand-Apte, J. A. Weatherbee, Y. Wang, F. Fang, J. G. Flanagan, M. L. Tsang, Het-erodimers of placenta growth factor/vascular endothelial growth factor. Endothelial activity, tumor cell expression, and high affinity binding to Flk-1/KDR. J. Biol. Chem. 271, 3154-3162 (1996). (Pubitemid 26060529)
35. R. Birkenhager, B. Schneppe, W. Rockl, J. Wilting, H. A. Weich, J. E. McCarthy, Synthesis and physiological activity of heterodimers comprising different splice forms of vascular endothelial growth factor and placenta growth factor. Biochem. J.316, 703-707 (1996). (Pubitemid 26278416)
36. A. Luttun, K. Brusselmans, H. Fukao, M. Tjwa, S. Ueshima, J. M. Herbert, O. Matsuo, D. Collen, P. Carmeliet, L. Moons, Loss of pla-cental growth factor protects mice against vascular permeability in pathological conditions. Biochem. Biophys. Res. Commun. 295, 428-434 (2002). (Pubitemid 34785852)
37. K. Aase, G. von Euler, X. Li, A. Ponten, P. Thoren, R. Cao, Y. Cao, B. Olofsson, S. Gebre-Medhin, M. Pekny, K. Alitalo, C. Betsholtz, U. Eriksson, Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect. Circulation104, 358-364 (2001). (Pubitemid 32666961)
38. A. Eriksson, R. Cao, R. Pawliuk, S. M. Berg, M. Tsang, D. Zhou, C. Fleet, K. Tritsaris, S. Dissing, P. Leboulch, Y. Cao, Placenta growth factor-1 antagonizes VEGF-induced angio-genesis and tumor growth by the formation of functionally inactive PlGF-1/VEGF hetero-dimers. Cancer Cell1, 99-108 (2002). (Pubitemid 41039180)
39. C. Fischer, B. Jonckx, M. Mazzone, S. Zac-chigna, S. Loges, L. Pattarini, E. Chorianopou-los, L. Liesenborghs, M. Koch, M. De Mol, M. Autiero, S. Wyns, S. Plaisance, L. Moons, N. van Rooijen, M. Giacca, J. M. Stassen, M. Dewerchin, D. Collen, P. Carmeliet, Anti-PlGF inhibits growth of VEGF(R)-inhibitor- resistant tumors without affecting healthy vessels. Cell 131, 463-475 (2007). (Pubitemid 350007692)
40. P. Carmeliet, L. Moons, A. Luttun, V. Vincenti, V. Compernolle, M. De Mol, Y. Wu, F. Bono, L. De-vy, H. Beck, D. Scholz, T. Acker, T. DiPalma, M. Dewerchin, A. Noel, I. Stalmans, A. Barra, S. Blacher, T. Vandendriessche, A. Ponten, U. Eriksson, K. H. Plate, J. M. Foidart, W. Schaper, D. S. Charnock-Jones, D. J. Hicklin, J. M. Herbert, D. Collen, M. G. Persico, Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogen-esis and plasma extravasation in pathological conditions. Nat. Med.7, 575-583 (2001). (Pubitemid 32448325)
41. M. Autiero, J. Waltenberger, D. Communi, A. Kranz, L. Moons, D. Lambrechts, J. Kroll, S. Plaisance, M. De Mol, F. Bono, S. Kliche, G. Fellbrich, K. Ballmer-Hofer, D. Maglione, U. Mayr-Beyrle, M. Dewerchin, S. Dombrowski, D. Stanimirovic, P. Van Hummelen, C. Dehio, D. J. Hicklin, G. Persico, J. M. Herbert, D. Com-muni, M. Shibuya, D. Collen, E. M. Conway, P. Carmeliet, Role of PlGF in the intra-and inter-molecular cross talk between the VEGF receptors Flt1 and Flk1. Nat. Med. 9, 936-943 (2003). (Pubitemid 36889938)
42. M. Shibuya, Differential roles of vascular en-dothelial growth factor receptor-1 and recep-tor-2 in angiogenesis. J. Biochem. Mol. Biol. 39, 469-478 (2006). (Pubitemid 44714526)
43. L. Seetharam, N. Gotoh, Y. Maru, G. Neufeld, S. Yamaguchi, M. Shibuya, A unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor VEGF. Oncogene10, 135-147 (1995).
44. J. Waltenberger, L. Claesson-Welsh, A. Sieg-bahn, M. Shibuya, C. H. Heldin, Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J. Biol. Chem. 269, 26988-26995 (1994). (Pubitemid 24332901)
45. R. L. Kendall, K. A. Thomas, Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc. Natl. Acad. Sci. U.S.A. 90, 10705-10709 (1993).
46. C. K. Goldman, R. L. Kendall, G. Cabrera, L. Soroceanu, Y. Heike, G. Y. Gillespie, G. P. Sie-gal, X. Mao, A. J. Bett, W. R. Huckle, K. A. Thomas, D. T. Curiel, Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate. Proc. Natl. Acad. Sci.U.S.A.95, 8795-8800 (1998). (Pubitemid 28350568)
47. N. Ferrara, H. Chen, T. Davis-Smyth, H. P. Ger-ber, T. N. Nguyen, D. Peers, V. Chisholm, K. J. Hillan, R. H. Schwall, Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat. Med.4, 336-340 (1998). (Pubitemid 28144094)
48. S. A. Cunningham, M. N. Waxham, P. M. Ar-rate, T. A. Brock, Interaction of the Flt-1 tyro-sine kinase receptor with the p85 subunit of phosphatidylinositol 3-kinase. Mapping of a novel site involved in binding. J. Biol. Chem. 270, 20254-20257 (1995).
49. A. Sawano, T. Takahashi, S. Yamaguchi, M. Shibuya, The phosphorylated 1169-tyrosine containing region of flt-1 kinase (VEGFR-1) is a major binding site for PLCgamma. Biochem. Biophys.Res.Commun.238, 487-491 (1997). (Pubitemid 27464413)
50. G. H. Fong, J. Rossant, M. Gertsenstein, M. L. Breitman, Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature376, 66-70 (1995).
51. J. Cai, S. Ahmad, W. G. Jiang, J. Huang, C. D. Kontos, M. Boulton, A. Ahmed, Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells. Diabetes 52, 2959-2968 (2003). (Pubitemid 37466866)
52. V. Tchaikovski, G. Fellbrich, J. Waltenberger, The molecular basis of VEGFR-1 signal trans-duction pathways in primary human mono-cytes. Arterioscler. Thromb. Vasc. Biol. 28, 322-328 (2008). (Pubitemid 351161206)
53. A. F. List, B. Glinsmann-Gibson, C. Stadheim, E. J. Meuillet, W. Bellamy, G. Powis, Vascular endothelial growth factor receptor-1 and re-ceptor-2 initiate a phosphatidylinositide 3-ki-nase-dependent clonogenic response in acute myeloid leukemia cells. Exp. Hematol. 32, 526-535 (2004). (Pubitemid 38739464)
54. E. Landgren, P. Schiller, Y. Cao, L. Claesson-Welsh, Placenta growth factor stimulates MAP kinase and mitogenicity but not phospholipase C-gamma and migration of endothelial cells expressing Flt 1. Oncogene 16, 359-367 (1998). (Pubitemid 28052290)
55. L. Bellik, M. C. Vinci, S. Filippi, F. Ledda, A. Parenti, Intracellular pathways triggered by the selective FLT-1-agonist placental growth factor in vascular smooth muscle cells exposed to hypoxia. Br. J. Pharmacol. 146, 568-575 (2005). (Pubitemid 41487073)
56. S. Hiratsuka, O. Minowa, J. Kuno, T. Noda, M. Shibuya, Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc. Natl. Acad. Sci. U.S.A.95, 9349-9354 (1998). (Pubitemid 28506234)
57. G. Viglietto, D. Maglione, M. Rambaldi, J. Cerutti, A. Romano, F. Trapasso, M. Fedele, P. Ippolito, G. Chiappetta, G. Botti, Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines. Oncogene 11, 1569-1579 (1995).
58. S. Grimmond, J. Lagercrantz, C. Drinkwater, G. Silins, S. Townson, P. Pollock, D. Gotley, E. Carson, S. Rakar, M. Nordenskjold, L. Ward, N. Hayward, G. Weber, Cloning and characterization of a novel human gene related to vascular endothelial growth factor. Genome Res. 6, 124-131 (1996). (Pubitemid 26111339)
59. B. Enholm, K. Paavonen, A. Ristimaki, V. Kumar, Y. Gunji, J. Klefstrom, L. Kivinen, M. Lai-ho, B. Olofsson, V. Joukov, U. Eriksson, K. Ali-talo, Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene 14, 2475-2483 (1997). (Pubitemid 27268166)
60. A. Slaven, A. R. Thornton, Neonatal otoacous-tic emissions recorded using maximum length sequence stimuli. Ear Hear. 19, 103-110 (1998). (Pubitemid 28164979)
61. D. Bellomo, J. P. Headrick, G. U. Silins, C. A. Paterson, P. S. Thomas, M. Gartside, A. Mould, M. M. Cahill, I. D. Tonks, S. M. Grimmond, S. Townson, C. Wells, M. Little, M. C. Cummings, N. K. Hayward, G. F. Kay, Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia. Circ. Res.86, E29-E35 (2000).
62. C. M. Failla, T. Odorisio, F. Cianfarani, C. Schi-etroma, P. Puddu, G. Zambruno, Placenta growth factor is induced in human ker-atinocytes during wound healing. J. Invest. Dermatol.115, 388-395 (2000).
63. C. J. Green, P. Lichtlen, N. T. Huynh, M. Yanovsky, K. R. Laderoute, W. Schaffner, B. J. Murphy, Placenta growth factor gene expression is induced by hypoxia in fibroblasts: A central role for metal transcription factor-1. Cancer Res.61, 2696-2703 (2001). (Pubitemid 32685857)
64. K. Hattori, B. Heissig, Y. Wu, S. Dias, R. Teja-da, B. Ferris, D. J. Hicklin, Z. Zhu, P. Bohlen, L. Witte, J. Hendrikx, N. R. Hackett, R. G. Crystal, M. A. Moore, Z. Werb, D. Lyden, S. Rafii, Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat. Med.8, 841-849 (2002).
65. M. Hollborn, S. Tenckhoff, M. Seifert, S. Kohler, P. Wiedemann, A. Bringmann, L. Kohen, Human retinal epithelium produces and responds to placenta growth factor. Graefes Arch. Clin. Exp. Ophthalmol.244, 732-741 (2006). (Pubitemid 43923196)
66. A. Luttun, M. Tjwa, L. Moons, Y. Wu, A. Angelil-lo-Scherrer, F. Liao, J. A. Nagy, A. Hooper, J. Priller, B. De Klerck, V. Compernolle, E. Daci, P. Bohlen, M. Dewerchin, J. M. Herbert, R. Fa-va, P. Matthys, G. Carmeliet, D. Collen, H. F. Dvorak, D. J. Hicklin, P. Carmeliet, Revascular-ization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat. Med. 8, 831-840 (2002).
67. D. Lyden, K. Hattori, S. Dias, C. Costa, P. Blaikie, L. Butros, A. Chadburn, B. Heissig, W. Marks, L. Witte, Y. Wu, D. Hicklin, Z. Zhu, N. R. Hackett, R. G. Crystal, M. A. Moore, K. A. Haj-jar, K. Manova, R. Benezra, S. Rafii, Impaired recruitment of bone-marrow-derived endothe-lial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat. Med. 7, 1194-1201 (2001). (Pubitemid 33063774)
68. N. Miyamoto, Y. de Kozak, J. C. Jeanny, A. Glotin, F. Mascarelli, P. Massin, D. BenEzra, F. Behar-Cohen, Placental growth factor-1 and epithelial haemato-retinal barrier breakdown: Potential implication in the pathogenesis of diabetic retinopathy. Diabetologia 50, 461-470 (2007).
69. C. Parr, G. Watkins, M. Boulton, J. Cai, W. G. Jiang, Placenta growth factor is over-expressed and has prognostic value in human breast cancer. Eur. J. Cancer 41, 2819-2827 (2005). (Pubitemid 41713119)
70. H. Yonekura, S. Sakurai, X. Liu, H. Migita, H. Wang, S.Yamagishi, M. Nomura, M. J. Abedin, H. Unoki, Y. Yamamoto, H. Yamamoto, Placenta growth factor and vascular endothelial growth factor B and C expression in microvas-cular endothelial cells and pericytes. Implication in autocrine and paracrine regulation of angiogenesis. J. Biol. Chem. 274, 35172-35178 (1999). (Pubitemid 129509573)
71. A. P. Taylor, L. Osorio, R. Craig, J. A. Raleigh, Z. Ying, D. M. Goldenberg, R. D. Blumenthal, Tumor-specific regulation of angiogenic growth factors and their receptors during recovery from cytotoxic therapy. Clin. Cancer Res.8, 1213-1222 (2002). (Pubitemid 35177377)
72. B. I. Rini, M. D. Michaelson, J. E. Rosenberg, R. M. Bukowski, J. A. Sosman, W. M. Stadler, T. E. Hutson, K. Margolin, C. S. Harmon, S. E. DePrimo, S. T. Kim, I. Chen, D. J. George, An-titumor activity and biomarker analysis of suni-tinib in patients with bevacizumab-refractory metastatic renal cell carcinoma. J. Clin. Oncol. 26, 3743-3748 (2008).
73. S. Hauser, H. A. Weich, A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta. Growth Factors 9, 259-268 (1993). (Pubitemid 24034347)
74. J. E. Park, H. H. Chen, J. Winer, K. A. Houck, N. Ferrara, Placenta growth factor. Potentia-tion of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J. Biol. Chem.269, 25646-25654 (1994). (Pubitemid 24982909)
75. W. P. Mutter, S. A. Karumanchi, Molecular mechanisms of preeclampsia. Microvasc. Res. 75, 1-8 (2008).
76. A. D. Nash, M. Baca, C. Wright, P. D. Scotney, The biology of vascular endothelial growth factor-B (VEGF-B). Pulm. Pharmacol. Ther. 19, 61-69 (2006). (Pubitemid 41606854)
77. Y. Li, F. Zhang, N. Nagai, Z. Tang, S. Zhang, P. Scotney, J. Lennartsson, C. Zhu, Y. Qu, C. Fang, J. Hua, O. Matsuo, G. H. Fong, H. Ding, Y. Cao, K. G. Becker, A. Nash, C. H. Heldin, X. Li, VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats. J. Clin. Invest.118, 913-923 (2008). (Pubitemid 351364599)
78. L. Cheng, H. Jia, M. Lohr, A. Bagherzadeh, D. I. Holmes, D. Selwood, I. Zachary, Anti-chemorepulsive effects of vascular endothelial growth factor and placental growth factor-2 in dorsal root ganglion neurons are mediated via neuropilin-1 and cyclooxygenase-derived prostanoid production. J. Biol. Chem. 279, 30654-30661 (2004). (Pubitemid 38937997)
79. M. Ziche, D. Maglione, D. Ribatti, L. Morbidelli, C. T. Lago, M. Battisti, I. Paoletti, A. Barra, M. Tucci, G. Parise, V. Vincenti, H. J. Granger, G. Viglietto, M. G. Persico, Placenta growth fac-tor-1 is chemotactic, mitogenic, and angio-genic. Lab. Invest.76, 517-531 (1997).
80. H. Kurz, J. Wilting, K. Sandau, B. Christ, Automated evaluation of angiogenic effects mediated by VEGF and PlGF homo-and het-erodimers. Microvasc. Res. 55, 92-102 (1998). (Pubitemid 28368416)
81. A. Adini, T. Kornaga, F. Firoozbakht, L. E. Benjamin, Placental growth factor is a survival factor for tumor endothelial cells and macrophages. Cancer Res. 62, 2749-2752 (2002). (Pubitemid 34525755)
82. Y. Cao, P. Linden, D. Shima, F. Browne, J. Folk-man, In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor/vascular endothelial growth factor. J. Clin. Invest.98, 2507-2511 (1996). (Pubitemid 26415071)
83. T. Schomber, L. Kopfstein, V. Djonov, I. Al-brecht, V. Baeriswyl, K. Strittmatter, G. Christo-fori, Placental growth factor-1 attenuates vascular endothelial growth factor-A-dependent tumor angiogenesis during beta cell carcino-genesis. Cancer Res. 67, 10840-10848 (2007). (Pubitemid 350145913)
84. L. Xu, D. M. Cochran, R. T. Tong, F. Winkler, S. Kashiwagi, R. K. Jain, D. Fukumura, Placenta growth factor overexpression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor ho-modimers in orthotopic mouse models. Cancer Res.66, 3971-3977 (2006).
85. F. Mac Gabhann, A. S. Popel, Dimerization of VEGF receptors and implications for signal transduction: A computational study. Biophys. Chem.128, 125-139 (2007). (Pubitemid 46843440)
86. Q. Pan, Y. Chanthery, W. C. Liang, S. Stawicki, J. Mak, N. Rathore, R. K. Tong, J. Kowalski, S. F. Yee, G. Pacheco, S. Ross, Z. Cheng, J. Le Couter, G. Plowman, F. Peale, A. W. Koch, Y. Wu, A. Bagri, M. Tessier-Lavigne, R. J. Watts, Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell11, 53-67 (2007). (Pubitemid 46054517)
87. F. Nishimoto, M. Sakata, R. Minekawa, Y. Okamoto, A. Miyake, A. Isobe, T. Yamamoto, T. Takeda, E. Ishida, K. Sawada, K. I. Morishige, T. Kimura, Metal transcription factor-1 is involved in hypoxia-dependent regulation of placenta growth factor in trophoblast-derived cells. Endocrinology, 10.1210/en.2008-0949 (2008).
88. L. Liu, G. P. Marti, X. Wei, X. Zhang, H. Zhang, Y. V. Liu, M. Nastai, G. L. Semenza, J. W. Harmon, Age-dependent impairment of HIF-1α expression in diabetic mice: Correction with electroporation-facilitated gene therapy increases wound healing, angiogenesis, and circulating angiogenic cells. J. Cell. Physiol. 217, 319-327 (2008).
89. J. M. Gleadle, B. L. Ebert, P. J. Ratcliffe, Diphenylene iodonium inhibits the induction of erythropoietin and other mammalian genes by hypoxia. Implications for the mechanism of oxygen sensing. Eur. J. Biochem. 234, 92-99 (1995).
90. T. Fujii, Y. Yonemitsu, M. Onimaru, M. Inoue, M. Hasegawa, H. Kuwano, K. Sueishi, VEGF function for upregulation of endogenous PlGF expression during FGF-2-mediated therapeutic angiogenesis. Atherosclerosis 200, 51-57 (2008).
91. T. Nakamura, H. Funayama, N. Kubo, T. Yasu, M. Kawakami, S. I. Momomura, S. E. Ishikawa, Elevation of plasma placental growth factor in the patients with ischemic cardiomyopathy. Int. J. Cardiol.131, 186-191 (2009).
92. L. Zhang, J. Chen, Y. Ke, R. E. Mansel, W. G. Jiang, Expression of placenta growth factor (PlGF) in non-small cell lung cancer (NSCLC) and the clinical and prognostic significance. World J. Surg. Oncol.3, 68 (2005). (Pubitemid 41554617)
93. S. C. Wei, P. N. Tsao, S. C. Yu, C. T. Shun, J. J. Tsai-Wu, C. H. Wu, Y. N. Su, F. J. Hsieh, J. M. Wong, Placenta growth factor expression is correlated with survival of patients with col-orectal cancer. Gut54, 666-672 (2005). (Pubitemid 40559252)
94. C. N. Chen, F. J. Hsieh, Y. M. Cheng, W. F. Cheng, Y. N. Su, K. J. Chang, P. H. Lee, The significance of placenta growth factor in angio-genesis and clinical outcome of human gastric cancer. Cancer Lett.213, 73-82 (2004). (Pubitemid 39118536)
95. M. He, K. Das, M. Blacksin, J. Benevenia, M. Hameed, A translocation involving the placen-tal growth factor gene is identified in an ep-ithelioid hemangioendothelioma. Cancer Genet.Cytogenet.168, 150-154 (2006).
96. M. C. Ho, C. N. Chen, H. Lee, F. J. Hsieh, C. T. Shun, C. L. Chang, Y. T. Lai, P. H. Lee, Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocel-lular carcinoma. Cancer Lett. 250, 237-249 (2007). (Pubitemid 46529444)
97. K. Matsumoto, K. Suzuki, H. Koike, M. Hasu-mi, H. Matsui, H. Okugi, Y. Shibata, K. Ito, H. Yamanaka, Placental growth factor gene expression in human prostate cancer and benign prostate hyperplasia. Anticancer Res.23, 3767-3773 (2003). (Pubitemid 37474323)
98. T. Odorisio, C. Schietroma, M. L. Zaccaria, F. Cianfarani, C. Tiveron, L. Tatangelo, C. M. Fail-la, G. Zambruno, Mice overexpressing placenta growth factor exhibit increased vasculariza-tion and vessel permeability. J. Cell Sci. 115, 2559-2567 (2002). (Pubitemid 34778073)
99. M. Marcellini, N. De Luca, T. Riccioni, A. Ciuc-ci, A. Orecchia, P. M. Lacal, F. Ruffini, M. Pesce, F. Cianfarani, G. Zambruno, A. Orlandi, C. M. Failla, Increased melanoma growth and metastasis spreading in mice overexpressing placenta growth factor. Am. J. Pathol. 169, 643-654 (2006). (Pubitemid 44156320)
100. B. Li, E. E. Sharpe, A. B. Maupin, A. A. Teleron, A. L. Pyle, P. Carmeliet, P. P. Young, VEGF and PlGF promote adult vasculogene-sis by enhancing EPC recruitment and vessel formation at the site of tumor neovasculariza-tion. FASEB J.20, 1495-1497 (2006). (Pubitemid 44961985)
101. A. P. Taylor, D. M. Goldenberg, Role of placenta growth factor in malignancy and evidence that an antagonistic PlGF/Flt-1 peptide inhibits the growth and metastasis of human breast cancer xenografts. Mol. Cancer Ther. 6, 524-531 (2007).
102. J. Chen, L. Ye, L. Zhang, W. G. Jiang, Placenta growth factor, PLGF, influences the motility of lung cancer cells, the role of Rho associated kinase, Rock1. J. Cell. Biochem.105, 313-320 (2008).
103. M. Bjorndahl, R. Cao, A. Eriksson, Y. Cao, Blockage of VEGF-induced angiogenesis by preventing VEGF secretion. Circ. Res. 94, 1443-1450 (2004). (Pubitemid 38780316)
104. J. Holash, S. Davis, N. Papadopoulos, S. D. Croll, L. Ho, M. Russell, P. Boland, R. Leidich, D. Hylton, E. Burova, E. Ioffe, T. Huang, C. Radziejewski, K. Bailey, J. P. Fandl, T. Daly, S. J. Wiegand, G. D. Yancopoulos, J. S. Rudge, VEGF-Trap: A VEGF blocker with potent anti-tumor effects. Proc. Natl. Acad. Sci. U.S.A.99, 11393-11398 (2002). (Pubitemid 34920936)
105. G. J. Riely, V. A. Miller, Vascular endothelial growth factor trap in non small cell lung cancer. Clin. Cancer Res. 13, 4623s-4627s (2007).
106. J. Dupont, M. L. Rothenberg, D. R. Spriggs, J. M. Cedarbaum, E. S. Furfine, D. P. Cohen, I. Dancy, H. S. Lee, W. Cooper, A. C. Lockhart, Safety and pharmacokinetics of intravenous VEGF Trap in a phase I clinical trial of patients with advanced solid tumors. J. Clin. Oncol. (Meet. Abstr.)23, 3029 (2005).
107. J. Dupont, L. Schwartz, J. Koutcher, D. Sprig-gs, M. Gordon, D. Mendelson, J. Murren, A. Lucarelli, J. Cedarbaum, Phase I and pharma-cokinetic study of VEGF Trap administered subcutaneously (sc) to patients (pts) with advanced solid malignancies. J. Clin. Oncol. (Meet. Abstr.)22, 3009 (2004).
108. E. Massarelli, V. A. Miller, N. B. Leighl, P. J. Rosen, K. S. Albain, L. L. Hart, O. Melnyk, L. Sternas, J. Ackerman, R. S. Herbst, Phase II study of the efficacy and safety of intravenous (IV) AVE0005 (VEGF Trap) given every 2 weeks in patients (Pts) with platinum-and er-lotinib-resistant adenocarcinoma of the lung (NSCLA). J. Clin. Oncol. (Meet. Abstr.) 25, 7627 (2007).
109. O. Rixe, C. Verslype, D. Khayat, S. Tejpar, B. Billemont, M. Crabbé, J. B. Méric, S. As-sadourian, E. Van Cutsem, A phase I dose escalation (DE) and pharmacokinetics (PK) study of intravenous aflibercept (VEGF Trap) plus irinotecan, 5-fluorouracil, and leucovorin (I-LV5FU2) in patients with advanced solid tumors (STs). J. Clin. Oncol. (Meet. Abstr.)26, 3557 (2008).
110. W. P. Tew, N. Colombo, I. Ray-Coquard, A. Oza, J. del Campo, G. Scambia, D. Spriggs, VEGF-Trap for patients (pts) with recurrent platinum-resistant epithelial ovarian cancer (EOC): Preliminary results of a randomized, multicenter phase II study. J. Clin. Oncol. (Meet. Abstr.)25, 5508 (2007).
111. J. F. De Groot, P. Y. Wen, K. Lamborn, S. Chang, T. F. Cloughesy, A. P. Chen, L. M. DeAngelis, M. P. Mehta, M. R. Gilbert, W. K. Yung, M. D. Prados, Phase II single arm trial of aflibercept in patients with recurrent temo-zolomide-resistant glioblastoma: NABTC 0601. J. Clin. Oncol. (Meet. Abstr.) 26, 2020 (2008).
112. P. Tang, S. J. Cohen, G. A. Bjarnason, C. Koll-mannsberger, K. Virik, M. J. MacKenzie, J. Brown, L. Wang, A. P. Chen, M. J. Moore, Phase II trial of aflibercept (VEGF Trap) in previously treated patients with metastatic col-orectal cancer (MCRC): A PMH phase II consortium trial. J. Clin. Oncol. (Meet. Abstr.) 26, 4027 (2008).
113. N. Isambert, G. Freyer, S. Zanetta, C. Fa-landry, K. Soussan Lazard, P. Fumoleau, A phase I dose escalation and pharmacokinetic (PK) study of intravenous aflibercept (VEGF trap) plus docetaxel (D) in patients (pts) with advanced solid tumors: Preliminary results. J. Clin. Oncol. (Meet. Abstr.)26, 3599 (2008).
114. A. Patnaik, M. Pipas, L. S. Rosen, L. Wood, K. Phipps, M. Mulay, C. Garay, M. Korc, J. Saran-topoulos, A phase I dose escalation and phar-macokinetic (PK) study of intravenous (iv) aflibercept (VEGF Trap) plus weekly gemc-itabine (Gem) in patients (pts) with advanced solid tumors: Preliminary results. J. Clin. Oncol. (Meet. Abstr.)26, 3558 (2008).
115. G. Freyer, P. Fumoleau, B. You, N. Isambert, P. Chevalier, V. Trillet Lenoir, A phase I dose escalation and pharmacokinetic (PK) study of intravenous (iv) aflibercept (VEGF Trap) plus docetaxel (D) and cisplatin (C) in patients (pts) with advanced solid tumors: Preliminary results. J. Clin. Oncol. (Meet. Abstr.)26, 14539 (2008).
116. S. Limentani, R. Just, A. Purdham, M. Mulay, A. Bair, J. F. Tamby, L. I. Chap, L. S. Rosen, A phase I dose escalation and pharmacokinetic (PK) study of intravenous (iv) aflibercept (VEGF Trap) plus FOLFOX4 in patients (pts) with advanced solid tumors: Preliminary results. J. Clin. Oncol. (Meet. Abstr.) 26, 3556 (2008).
117. N. Ferrara, K. Carver-Moore, H. Chen, M. Dowd, L. Lu, K. S. O'Shea, L. Powell-Braxton, K. J. Hillan, M. W. Moore, Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.Nature380, 439-442 (1996). (Pubitemid 26102720)
118. P. Carmeliet, V. Ferreira, G. Breier, S. Polle-feyt, L. Kieckens, M. Gertsenstein, M. Fahrig, A. Vandenhoeck, K. Harpal, C. Eberhardt, C. Declercq, J. Pawling, L. Moons, D. Collen, W. Risau, A. Nagy, Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380, 435-439 (1996). (Pubitemid 26102719)
119. N. W. Gale, M. G. Dominguez, I. Noguera, L. Pan, V. Hughes, D. M.
120. C. M. Witt, W. J. Won, V. Hurez, C. A. Klug, Notch2 haploinsufficiency results in diminished B1 B cells and a severe reduction in marginal zone B cells. J. Immunol. 171, 2783-2788 (2003). (Pubitemid 37093496)
121. A. Luttun, M. Tjwa, P. Carmeliet, Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): Novel therapeutic targets for an-giogenic disorders. Ann. N.Y. Acad. Sci. 979, 80-93 (2002). (Pubitemid 36121141)
122. A. C. Schuh, P. Faloon, Q. L. Hu, M. Bhimani, K. Choi, In vitro hematopoietic and endothelial potential of flk-1(-/-) embryonic stem cells and embryos. Proc. Natl. Acad. Sci. U.S.A.96, 2159-2164 (1999). (Pubitemid 29117884)
123. K. Sasaki, H. Yagi, R. T. Bronson, K. Tominaga, T. Matsunashi, K. Deguchi, Y. Tani, T. Kishimo-to, T. Komori, Absence of fetal liver hematopoiesis in mice deficient in transcrip-tional coactivator core binding factor beta. Proc. Natl. Acad. Sci. U.S.A. 93, 12359-12363 (1996). (Pubitemid 26367148)
124. S. Hiratsuka, Y. Maru, A. Okada, M. Seiki, T. Noda, M. Shibuya, Involvement of Flt-1 tyro-sine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis. Cancer Res.61, 1207-1213 (2001). (Pubitemid 32174444)
125. S. Hiratsuka, K. Nakamura, S. Iwai, M. Murakami, T. Itoh, H. Kijima, J. M. Shipley, R. M. Senior, M. Shibuya, MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2, 289-300 (2002). (Pubitemid 41043963)
126. M. Murakami, S. Iwai, S. Hiratsuka, M. Ya-mauchi, K. Nakamura, Y. Iwakura, M. Shibuya, Signaling of vascular endothelial growth factor receptor-1 tyrosine kinase promotes rheumatoid arthritis through activation of monocytes/macrophages. Blood 108, 1849-1856 (2006). (Pubitemid 44394993)
127. J. Kami, K. Muranaka, Y. Yanagi, R. Obata, Y. Tamaki, M. Shibuya, Inhibition of choroidal neovascularization by blocking vascular en-dothelial growth factor receptor tyrosine ki-nase. Jpn. J. Ophthalmol.52, 91-98 (2008). (Pubitemid 351624401)
128. M. Kerber, Y. Reiss, A. Wickersheim, M. Ju-gold, F. Kiessling, M. Heil, V. Tchaikovski, J. Waltenberger, M. Shibuya, K. H. Plate, M. R. Machein, Flt-1 signaling in macrophages promotes glioma growth in vivo. Cancer Res. 68, 7342-7351 (2008).
129. J. M. Ebos, C. R. Lee, J. G. Christensen, A. J. Mutsaers, R. S. Kerbel, Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proc. Natl. Acad. Sci. U.S.A.104, 17069-17074 (2007).
130. Y. Shaked, G. Bocci, R. Munoz, S. Man, J. M. Ebos, D. J. Hicklin, F. Bertolini, R. D'Amato, R. S. Kerbel, Cellular and molecular surrogate markers to monitor targeted and non-targeted antiangiogenic drug activity and determine optimal biologic dose. Curr. Cancer Drug Targets 5, 551-559 (2005). (Pubitemid 41502566)
131. M. I. Dorrell, E. Aguilar, L. Scheppke, F. H. Bar-nett, M. Friedlander, Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. Proc. Natl. Acad. Sci. U.S.A. 104, 967-972 (2007). (Pubitemid 46154720)
132. J. Folkman, Is angiogenesis an organizing principle in biology and medicine? J. Pediatr. Surg.42, 1-11 (2007) (Pubitemid 46043358)