Biochemistry (Moscow)

, 73:751 | Cite as

Mechanisms of angiogenesis

Review

Abstract

Tissue activity of angiogenesis depends on the balance of many stimulating or inhibiting factors. The key signaling system that regulates proliferation and migration of endothelial cells forming the basis of any vessel are vascular endothelium growth factors (VEGF) and their receptors. The VEGF-dependent signaling system is necessary for formation of the embryonic vascular system. Neoangiogenesis during tumor growth is also associated with activation of this signaling system. The biological significance of the effect of such system on the cells depends on the content in tissue of various factors of the VEGF family and their receptors, while in the case of VEGFA it is defined by the ratio of different isoforms of this growth factor. A number of other signaling systems are also involved in regulation of the main steps of vessel formation. The signaling system D114/Notch regulates selection of endothelial cells for beginning of angiogenic expansion by endowing particular properties to endothelial cells leading in this process. An important step in vessel stabilization and maturation is vascular wall formation. Signaling system PDGFB/PDGFRß as well as angiopoietins Ang1, Ang2, and their receptor Tie2 are involved in recruiting mural cells (pericytes and smooth muscle cells). Identification of key molecules involved in the regulation of angiogenesis may provide new possibilities for development of drugs suitable for inhibition of angiogenesis or its stimulation in various pathologies.

Key words

angiogenesis vascular endothelium growth factors (VEGF) neuropilins PDGFB angiopoietins 

Abbreviations

a.a.

amino acid residues

Ang

angiopoietins

EGF

epidermal growth factor

FGF

fibroblast growth factor

PDGF

platelet-derived growth factor

PlGF

placental growth factor

RTK

receptor tyrosine kinases

TGF

transforming growth factor

VEGF

vascular endothelium growth factor

VEGFR

vascular endothelium growth factor receptor

References

  1. 1.
    Coultas, L., Chawengsaksophak, K., and Rossant, J. (2005) Nature, 438, 937–945.PubMedCrossRefGoogle Scholar
  2. 2.
    Gerhardt, H., and Betsholtz, C. (2003) Cell Tissue Res., 314, 15–23.PubMedCrossRefGoogle Scholar
  3. 3.
    Folkman, J. (1990) J. Natl. Cancer Inst., 82, 4.PubMedCrossRefGoogle Scholar
  4. 4.
    Folkman, J. (1995) N. Engl. J. Med., 333, 1757–1763.PubMedCrossRefGoogle Scholar
  5. 5.
    Ferrara, N., and Davis-Smyth, T. (1997) Endocr. Rev., 18, 4–25.PubMedCrossRefGoogle Scholar
  6. 6.
    Leung, D. W., Cachianes, G., Kuang, W. J., Goeddel, D. V., and Ferrara, N. (1989) Science, 246, 1306–1309.PubMedCrossRefGoogle Scholar
  7. 7.
    Nagy, J. A., Vasile, E., Feng, D., Sundberg, C., Brown, L. F., Detmar, M. J., Lawitts, J. A., Benjamin, L., Tan, X., Manseau, E. J., Dvorak, A. M., and Dvorak, H. F. (2002) J. Exp. Med., 196, 1497–1506.PubMedCrossRefGoogle Scholar
  8. 8.
    Gerber, H. P., Dixit, V., and Ferrara, N. (1998) J. Biol. Chem., 273, 13313–13316.PubMedCrossRefGoogle Scholar
  9. 9.
    Gerber, H. P., McMurtrey, A., Kowalski, J., Yan, M., Keyt, B. A., Dixit, V., and Ferrara, N. (1998) J. Biol. Chem., 273, 30366–30343.CrossRefGoogle Scholar
  10. 10.
    Benjamin, L. E., Golijanin, D., Itin, A., Pode, D., and Keshet, E. (1999) J. Clin. Invest., 103, 159–165.PubMedCrossRefGoogle Scholar
  11. 11.
    Gerber, H. P., Hillan, K. J., Ryan, A. M., Kowalski, J., Keller, G. A., Rangell, L., Wright, B. D., Radtke, F., Aguet, M., and Ferrara, N. (1999) Development, 126, 1149–1159.PubMedGoogle Scholar
  12. 12.
    Senger, D. R., Galli, S. J., Dvorak, A. M., Perruzzi, C. A., Harvey, V. S., and Dvorak, H. F. (1983) Science, 219, 983–985.PubMedCrossRefGoogle Scholar
  13. 13.
    Dvorak, H. F., Brown, L. F., Detmar, L., and Dvorak, A. M. (1995) Am. J. Pathol., 146, 1029–1039.PubMedGoogle Scholar
  14. 14.
    Houck, K. A., Ferrara, N., Winer, J., Cachianes, G., Li, B., and Leung, D. W. (1991) Mol. Endocrinol., 5, 1806–1814.PubMedCrossRefGoogle Scholar
  15. 15.
    Tischer, E., Mitchell, R., Hartman, T., Silva, M., Gospodarowicz, D., Fiddes, J. C., and Abraham, J. A. (1991) J. Biol. Chem., 266, 11947–11954.PubMedGoogle Scholar
  16. 16.
    Ferrara, N., and Henzel, W. J. (1989) Biochem. Biophys. Res. Commun., 161, 851–858.PubMedCrossRefGoogle Scholar
  17. 17.
    Houck, K. A., Leung, D. W., Rowland, A. M., Winer, J., and Ferrara, N. (1992) J. Biol. Chem., 267, 26031–26037.PubMedGoogle Scholar
  18. 18.
    Park, J. E., Keller, H.-A., and Ferrara, N. (1993) Mol. Biol. Cell, 4, 1317–1326.PubMedGoogle Scholar
  19. 19.
    Keyt, B. A., Berleau, L. T., Nguyen, H. V., Chen, H., Heinsohn, H., Vandlen, R., and Ferrara, N. (1996) J. Biol. Chem., 271, 7788–7795.PubMedCrossRefGoogle Scholar
  20. 20.
    Carmeliet, P., Ng, Y.-S., Nuyens, D., Theilmeier, G., Brusselmans, K., Cornelissen, I., Ehler, E., Kakkar, V. V., Stalmans, I., Mattot, V., Perriard, J.-C., Dewerchin, M., Flameng, W., Nagy, A., Lupu, F., Moons, L., Collen, D., D’Amore, P. A., and Shima, D. T. (1999) Nat. Med., 5, 495–502.PubMedCrossRefGoogle Scholar
  21. 21.
    Dor, Y., Porat, R., and Keshet, E. (2001) Am. J. Physiol. Cell Physiol., 280, C1367–C1374.PubMedGoogle Scholar
  22. 22.
    Neufeld, G., Cohen, T., Gengrinovitch, S., and Poltorak, Z. (1999) FASEB J., 13, 9–22.PubMedGoogle Scholar
  23. 23.
    De Vries, C., Escobedo, J. A., Ueno, H., Houck, K., Ferrara, N., and Williams, L. T. (1992) Science, 255, 989–991.PubMedCrossRefGoogle Scholar
  24. 24.
    Shibuya, M., Yamaguchi, S., Yamane, A., Ikeda, T., Tojo, A., Matsushime, H., and Sato, M. (1990) Oncogene, 5, 519–524.PubMedGoogle Scholar
  25. 25.
    Terman, B. I., Carrion, M. E., Kovacs, E., Rasmussen, B. A., Eddy, R., and Shows, T. B. (1991) Oncogene, 6, 1677–1683.PubMedGoogle Scholar
  26. 26.
    Matthews, W., Jordan, C. T., Gavin, M., Jenkins, N. A., Copeland, N. G., and Lemischka, I. R. (1991) Proc. Natl. Acad. Sci. USA, 88, 9026–9030.PubMedCrossRefGoogle Scholar
  27. 27.
    Millauer, B., Wizigmann-Voos, S., Schnurch, H., Martinez, R., Moller, N. P. H., Risau, W., and Ullrich, A. (1993) Cell, 72, 835–846.PubMedCrossRefGoogle Scholar
  28. 28.
    Galland, F., Karamysheva, A., Pebusque, M. J., Borg, J. P., Rottapel, R., Dubreuil, P., Rosnet, O., and Birnbaum, D. (1993) Oncogene, 8, 1233–1240.PubMedGoogle Scholar
  29. 29.
    Pajusola, K., Aprelikova, O., Kohronen, J., Kaipainen, A., Petrovaara, L., Alitalo, R., and Alitalo, K. (1992) Cancer. Res., 52, 5738–5743.PubMedGoogle Scholar
  30. 30.
    Alitalo, K., and Carmeliet, P. (2002) Cancer Cell, 1, 219–227.PubMedCrossRefGoogle Scholar
  31. 31.
    Sawano, A., Takahashi, T., Yamaguchi, S., Aonuma, M., and Shibuya, M. (1996) Cell Growth Differ., 7, 213–221.PubMedGoogle Scholar
  32. 32.
    Terman, B. I., Dougher-Vermazen, M., Carrion, M. E., Dimitrov, D., Armaltno, D. C., Gospodarowicz, D., and Bohlen, P. (1992) Biochem. Biophys. Res. Commun., 187, 1579–1586.PubMedCrossRefGoogle Scholar
  33. 33.
    Waltenberger, J., Claesson-Welsh, L., Siegbahn, A., Shibuya, M., and Heldin, C. H. (1994) J. Biol. Chem., 269, 26988–26995.PubMedGoogle Scholar
  34. 34.
    Seetharam, L., Gotoh, N., Maru, Y., Neufeld, G., Yamaguchi, S., and Shibuya, M. (1995) Oncogene, 10, 135–147.PubMedGoogle Scholar
  35. 35.
    Hiratsuka, S., Minowa, O., Kuno, J., Noda, T., and Shibuya, M. (1998) Proc. Natl. Acad. Sci. USA, 95, 9349–9354.PubMedCrossRefGoogle Scholar
  36. 36.
    Park, J. E., Chen, H. H., Winer, J., Houck, K. A., and Ferrara, N. (1994) J. Biol. Chem., 269, 25646–25654.PubMedGoogle Scholar
  37. 37.
    Kendall, R. L., and Thomas, K. A. (1993) Proc. Natl. Acad. Sci. USA, 90, 10705–10709.PubMedCrossRefGoogle Scholar
  38. 38.
    Fong, G. H., Rossant, J., Gertsentein, M., and Breitman, M. L. (1995) Nature, 376, 66–70.PubMedCrossRefGoogle Scholar
  39. 39.
    Stacker, S. A., Vitali, A., Caesar, C., Domagala, T., Groenen, L., Nice, E., Achen, M. A., and Wilks, A. F. (1999) J. Biol. Chem., 274, 34884–34892.PubMedCrossRefGoogle Scholar
  40. 40.
    Olofsson, B., Korpelainen, E., Pepper, M. S., Mandriota, S. J., Aase, K., Kumar, V., Gunji, Y., Jeltsch, M. M., Shibuya, M., Alitalo, K., and Eriksson, U. (1998) Proc. Natl. Acad. Sci. USA, 95, 11709–11714.PubMedCrossRefGoogle Scholar
  41. 41.
    Shalaby, F., Rossant, J., Yamaguchi, T. P., Gertsenstein, M., Wu, X. F., Breitman, M. L., and Schuh, A. C. (1995) Nature, 376, 62–66.PubMedCrossRefGoogle Scholar
  42. 42.
    Eichmann, A., Corbel, C., Nataf, V., Vaigot, P., Breant, C., and le Douarin, N. M. (1997) Proc. Natl. Acad. Sci. USA, 94, 5141–5146.PubMedCrossRefGoogle Scholar
  43. 43.
    Lyttle, D. J., Fraser, K. M., Fleming, S. B., Mercer, A. A., and Robinson, A. J. (1994) J. Virol., 68, 84–92.PubMedGoogle Scholar
  44. 44.
    Millauer, B., Shawver, L. K., Plate, K. H., Risau, W., and Ullrich, A. (1994) Nature, 367, 567–579.CrossRefGoogle Scholar
  45. 45.
    Scobe, M., Rockwell, P., Goldstein, N., Vosseler, S., and Fusenig, N. E. (1997) Nat. Med., 3, 1222–1227.CrossRefGoogle Scholar
  46. 46.
    Meyer, M., Clauss, M., Lepple-Wienhues, A., Waltenberger, J., Augustin, H. G., Ziche, M., Lanz, C., Buttner, M., Rziha, H. J., and Dehio, C. (1999) EMBO J., 18, 363–374.PubMedCrossRefGoogle Scholar
  47. 47.
    Wise, L. M., Veikkola, T., Mercer, A. A., Savory, L. J., Fleming, S. B., Caesar, C., Vitali, A., Makinen, T., Alitalo, K., and Stacker, S. A. (1999) Proc. Natl. Acad. Sci. USA, 96, 3071–3076.PubMedCrossRefGoogle Scholar
  48. 48.
    Larcher, F., Murillas, R., Bolontrade, M., Conti, C. J., and Jorcano, J. L. (1998) Oncogene, 17, 303–311.PubMedCrossRefGoogle Scholar
  49. 49.
    Shibuya, M. (2006) J. Biochem. Mol. Biol., 39, 469–478.PubMedGoogle Scholar
  50. 50.
    Jia, H., Bagherzadeh, A., Bicknell, R., Duchen, M. R., Liu, D., and Zachary, I. (2004) J. Biol. Chem., 279, 36148–36157.PubMedCrossRefGoogle Scholar
  51. 51.
    Makinen, T., Veikkola, T., Mustjoki, S., Karpanen, T., Catimel, B., Nice, E. C., Wise, L., Mercer, A., Kowalski, H., Kerjaschki, D., Stacker, S. A., Achen, M. G., and Alitalo, K. (2001) EMBO J., 20, 4762–4773.PubMedCrossRefGoogle Scholar
  52. 52.
    Lee, J., Gray, A., Yuan, J., Luoh, S.-M., Avraham, H., and Wood, W. I. (1996) Proc. Natl. Acad. Sci. USA, 93, 1988–1992.PubMedCrossRefGoogle Scholar
  53. 53.
    Yamada, Y., Nezu, J., Shimane, M., and Hirata, Y. (1997) Genomics, 42, 483–488.PubMedCrossRefGoogle Scholar
  54. 54.
    Achen, M. G., Jeltsch, M., Kukk, E., Makinen, T., Vitali, A., Wilks, A. F., Alitalo, K., and Stacker, S. A. (1998) Proc. Natl. Acad. Sci. USA, 95, 548–553.PubMedCrossRefGoogle Scholar
  55. 55.
    Karkkainen, M. J., Haiko, P., Sainio K., Partanen, J., Taipale, J., Petrova, T. V., Jeltsch, M., Jackson, D. G., Talikka, M., Rauvala, H., Betsholtz, C., and Alitalo, K. (2004) Nature Immunol., 5, 74–80.CrossRefGoogle Scholar
  56. 56.
    Baldwin, M. E., Halford, M. M., Roufail, S., Williams, R. A., Hibbs, M. L., Grail, D., Kubo, H., Stacker, S. A., and Achen, M. G. (2005) Mol. Cell. Biol., 25, 2441–2449.PubMedCrossRefGoogle Scholar
  57. 57.
    Joukov, V., Sorsa, T., Kumar, V., Jeltsch, M., Claesson-Welsh, L., Cao, Y., Saksela, O., Kalkkinen, N., and Alitalo, K. (1997) EMBO J., 16, 3898–3911.PubMedCrossRefGoogle Scholar
  58. 58.
    Stacker, S. A., Stenvers, K., Caesar, C., Vitali, A., Domagala, T., Nice, E., Roufail, S., Simpson, R. J., Moritz, R., Karpanen, T., Alitalo, K., and Achen, M. G. (1999) J. Biol. Chem., 274, 32127–32136.PubMedCrossRefGoogle Scholar
  59. 59.
    Dixelius, J., Makinen, T., Wirzenius, M., Karkkainen, M. J., Wernstedt, C., Alitalo, K., and Claesson-Welsh, L. (2003) J. Biol. Chem., 278, 40973–40979.PubMedCrossRefGoogle Scholar
  60. 60.
    Shushanov, S. S., Bronstein, M. I., Adelaide, J., Jussila, L., Tchipysheva, T., Jacquemier, J., Stavrovskaya, A., Birnbaum, D., and Karamysheva, A. (2000) Int. J. Cancer, 86, 47–52.PubMedCrossRefGoogle Scholar
  61. 61.
    Soker, S., Takashima, S., Miao, H. Q., Neufeld, G., and Klagsbrun, M. (1998) Cell, 92, 735–745.PubMedCrossRefGoogle Scholar
  62. 62.
    Klagsbrun, M., Takashima, S., and Mamluk, R. (2002) Adv. Exp. Med. Biol., 515, 33–48.PubMedGoogle Scholar
  63. 63.
    Neufeld, G., Cohen, T., Shraga, N., Lange, T., Kessler, O., and Herzog, Y. (2002) Trends Cardiovasc. Med., 12, 13–19.PubMedCrossRefGoogle Scholar
  64. 64.
    Kawasaki, T., Kitsukawa, T., Bekku, Y., Matsuda, Y., Sanbo, M., Yagi, T., and Fujisawa, H. (1999) Development, 126, 4895–4902.PubMedGoogle Scholar
  65. 65.
    Yuan, L., Moyon, D., Pardanaud, L., Breant, C., Karkkainen, M. J., Alitalo, K., and Eichmann, A. (2002) Development, 129, 4797–4806.PubMedGoogle Scholar
  66. 66.
    Stalmans, I., Ng, Y.-S., Rohan, R., Fruttiger, M., Bouche, A., Yuce, A., Fujisawa, H., Hermans, B., Shani, M., Jansen, S., Hicklin, D., Anderson, D. J., Gardiner, T., Hammes, H.-P., Moons, L., Dewerchin, M., Collen, D., Carmeliet, P., and D’Amore, P. A. (2002) J. Clin. Invest., 109, 327–336.PubMedGoogle Scholar
  67. 67.
    Gu, C., Rodriguez, E. R., Reimert, D. V., Shu, T., Fritzsch, B., Richards, L. J., Kolodkin, A. L., and Ginty, D. D. (2003) Dev. Cell, 5, 45–57.PubMedCrossRefGoogle Scholar
  68. 68.
    Karpanen, T., Heckman, C. A., Keskitalo, S., Jeltsch, M., Ollila, H., Neufeld, G., Tamagnone, L., and Alitalo, K. (2006) FASEB J., 20, 1462–1472.PubMedCrossRefGoogle Scholar
  69. 69.
    Lee, S., Jilani, S. M., Nikolova, G. V., Carpizo, D., and Iruela-Arispe, M. L. (2005) J. Cell Biol., 169, 681–691.PubMedCrossRefGoogle Scholar
  70. 70.
    Ladomery, M. R., Harper, S. J., and Bates, D. O. (2006) Cancer Lett., 249, 133–142.PubMedCrossRefGoogle Scholar
  71. 71.
    Sainson, R. C., Aoto, J., Nakatsu, M. N., Holderfield, M., Conn, E., Koller, E., and Hughes, C. C. W. (2005) FASEB. J., 19, 1027–1029.PubMedGoogle Scholar
  72. 72.
    Uyttendaele, H., Ho, J., Rossant, J., and Kitajewski, J. (2001) Proc. Natl. Acad. Sci. USA, 98, 5643–5648.PubMedCrossRefGoogle Scholar
  73. 73.
    Radtke, F., Schweisguth, F., and Pear, W. (2005) EMBO. Rep., 6, 1120–1125.PubMedCrossRefGoogle Scholar
  74. 74.
    Le Borgne, R., Bardin, A., and Schweisguth, F. (2005) Development, 132, 1751–1762.PubMedCrossRefGoogle Scholar
  75. 75.
    Fortini, M. E. (2002) Nat. Rev. Mol. Cell. Biol., 3, 673–684.PubMedCrossRefGoogle Scholar
  76. 76.
    Shutter, J. R., Scully, S., Fan, W., Richards, W. G., Kitajewski, J., Deblandre, G. A., Kintner, C. R., and Stark, K. L. (2000) Genes Dev., 14, 1313–1318.PubMedGoogle Scholar
  77. 77.
    Krebs, L. T., Xue, Y., Norton, C. R., Shutter, J. R., Maguire, M., Sundberg, J. P., Gallahan, D., Closson, V., Kitajewski, J., Callahan, R., Smith, G. H., Stark, K. L., and Gridley, T. (2000) Genes Dev., 14, 1343–1352.PubMedGoogle Scholar
  78. 78.
    Gale, N. W., Dominguez, M. G., Noguera, I., Pan, L., Hughes, V., Valenzuela, D. M., Murphy, A. J., Adams, N. C., Lin, H. C., Holash, J., Thurston, G., and Yancopoulos, G. D. (2004) Proc. Natl. Acad. Sci. USA, 101, 15949–15954.PubMedCrossRefGoogle Scholar
  79. 79.
    Benedito, R., and Duarte, A. (2005) Gene Exp. Patterns, 5, 750–755.CrossRefGoogle Scholar
  80. 80.
    Duarte, A., Hirashima, M., Benedito, R., Trindade, A., Diniz, P., Bekman, E., Costa, L., Henrique, D., and Rossant, J. (2004) Genes Dev., 18, 2474–2478.PubMedCrossRefGoogle Scholar
  81. 81.
    Krebs, L. T., Shutter, J. R., Tanigaki, K., Honjo, T., Stark, K. L., and Gridley, T. (2004) Genes Dev., 18, 2469–2473.PubMedCrossRefGoogle Scholar
  82. 82.
    Carmeliet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kieckens, L., Gertsenstein, M., Fahrig, M., Vandenhoeck, A., Harpal, K., Eberhardt, C., Declercq, C., Pawling, J., Moons, L., Collen, D., Risau, W., and Nagy, A. (1996) Nature, 380, 435–439.PubMedCrossRefGoogle Scholar
  83. 83.
    Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’shea, K. S., Powell-Braxton, L., Hillan, K. J., and Moore, M. W. (1996) Nature, 380, 439–442.PubMedCrossRefGoogle Scholar
  84. 84.
    Liu, Z., Shirakawa, T., Li, Y., Soma, A., Oka, M., Dotto, G. P., Fairman, R. M., Velazquez, O. C., and Herlyn, M. (2003) Mol. Cell. Biol., 23, 14–25.PubMedCrossRefGoogle Scholar
  85. 85.
    Hellstrom, M., Phng L., Hofmann, J. J., Wallgard, E., Coultas, L., Lindblom, P., Alva, J., Nilsson, A., Karlsson, L., Gaiano, N., Yoon, K., Rossant, J., Iruela-Arispe, M. L., Kalen, M., Gerhardt, H., and Betsholtz, C. (2007) Nature, 445, 776–780.PubMedCrossRefGoogle Scholar
  86. 86.
    Suchting, S., Freitas, C., Noble, F., Benedito, R., Breant, C., Duarte, A., and Eichmann, A. (2007) Proc. Natl. Acad. Sci. USA, 104, 3225–3230.PubMedCrossRefGoogle Scholar
  87. 87.
    Siekmann, A. F., and Lawson, N. D. (2007) Nature, 445, 781–784.PubMedCrossRefGoogle Scholar
  88. 88.
    Williams, C. K., Li, J., Murga, M., Harris, A. L., and Tosato, G. (2006) Blood, 107, 931–939.PubMedCrossRefGoogle Scholar
  89. 89.
    Ridgway, J., Zhang, G., Wu, Y., Stawicki, S., Liang, W.-C., Chanthery, Y., Kowalski, J., Watts, R. J., Callahan, C., Kasman, I., Singh, M., Chien, M., Tan, C., Hongo, J.-A. S., Sauvage, F., Plowman, G., and Yan, M. (2006) Nature, 444, 1083–1087.PubMedCrossRefGoogle Scholar
  90. 90.
    Noguera-Troise, I., Daly, C., Papadopoulos, N. J., Coetzee, S., Boland, P., Gale, N. W., Lin, H. C., Yancopoulos, G. D., and Thurston, G. (2006) Nature, 444, 1032–1037.PubMedCrossRefGoogle Scholar
  91. 91.
    Lobov, I. B., Renard, R. A., Papadopoulos, N., Gale, N. W., Thurston, G., Yancopoulos, G. D., and Wiegand, S. J. (2007) Proc. Natl. Acad. Sci. USA, 104, 3219–3224.PubMedCrossRefGoogle Scholar
  92. 92.
    Gerhardt, H., Golding, M., Fruttiger, M., Ruhrberg, C., Lundkvist, A., Abramsson, A., Jeltsch, M., Mitchell, C., Alitalo, K., Shima, D., and Betsholtz, C. J. (2003) Cell. Biol., 161, 1163–1177.CrossRefGoogle Scholar
  93. 93.
    Jain, R. K. (2003) Nature Med., 9, 685–693.PubMedCrossRefGoogle Scholar
  94. 94.
    Cleaver, O., and Melton, D. A. (2003) Nature Med., 9, 661–668.PubMedCrossRefGoogle Scholar
  95. 95.
    Baluk, P., Hashizume, H., and McDonald, D. M. (2005) Curr. Opin. Genet. Dev., 15, 102–111.PubMedCrossRefGoogle Scholar
  96. 96.
    Jain, R. K. (2005) Science, 307, 58–62.PubMedCrossRefGoogle Scholar
  97. 97.
    Carmeliet, P., and Jain, R. K. (2000) Nature, 407, 249–257.PubMedCrossRefGoogle Scholar
  98. 98.
    Ferrara, N., and Kerbel, R. S. (2005) Nature, 438, 967–974.PubMedCrossRefGoogle Scholar
  99. 99.
    Betsholtz, C. (2004) Cytokine Growth Factor Rev., 15, 215–228.PubMedCrossRefGoogle Scholar
  100. 100.
    Lindahl, P., Johansson, B. R., Leveen, P., and Betsholtz, C. (1997) Science, 277, 242–245.PubMedCrossRefGoogle Scholar
  101. 101.
    Fredriksson, L., Li, H., and Eriksson, U. (2004) Cytokine. Growth Factor Rev., 15, 197–204.PubMedCrossRefGoogle Scholar
  102. 102.
    Holmes, D. I., and Zachary, I. (2005) Genome Biol., 6, 209–219.PubMedCrossRefGoogle Scholar
  103. 103.
    Kondo, K., Hiratuska, S., Subbalakshmi, E., Matsushime, H., and Shibuya, M. (1998) Gene, 208, 297–305.PubMedCrossRefGoogle Scholar
  104. 104.
    Reigstad, L. J., Varhaug, J. E., and Lillehaug, J. R. (2005) FEBS J., 272, 5723–5741.PubMedCrossRefGoogle Scholar
  105. 105.
    Bergers, G., and Song, S. (2005) Neurooncology, 7, 452–464.Google Scholar
  106. 106.
    Westermark, B., and Heldin, C. H. (1993) Acta Oncol., 32, 101–105.PubMedCrossRefGoogle Scholar
  107. 107.
    Soriano, P. (1997) Development, 124, 2691–2700.PubMedGoogle Scholar
  108. 108.
    Hellstrom, M., Kalen, M., Lindahl, P., Abramsson, A., and Betsholtz, C. (1999) Development, 126, 3047–3055.PubMedGoogle Scholar
  109. 109.
    Hirschi, K. K., Rohovsky, S. A., Beck, L. H., Smith, S. R., and D’Amore, P. A. (1999) Circ. Res., 84, 298–305.PubMedGoogle Scholar
  110. 110.
    Armulik, A., Abramsson, A., and Betsholtz, C. (2005) Circ. Res., 97, 512–523.PubMedCrossRefGoogle Scholar
  111. 111.
    Enge, M., Bjarnegard, M., Gerhardt, H., Gustafsson, E., Kalen, M., Asker, N., Hammes, H. P., Shani, M., Fassler, R., and Betsholtz, C. (2002) EMBO J., 21, 4307–4316.PubMedCrossRefGoogle Scholar
  112. 112.
    Hirschi, K. K., Rohovsky, S. A., and D’Amore, P. A. (1998) J. Cell Biol., 141, 805–814.PubMedCrossRefGoogle Scholar
  113. 113.
    Sims, D. E. (2000) Clin. Exp. Pharmacol. Physiol., 27, 842–846.PubMedCrossRefGoogle Scholar
  114. 114.
    Orlidge, A., and D’Amore, P. A. (1987) J. Cell. Biol., 105, 1455–1462.PubMedCrossRefGoogle Scholar
  115. 115.
    Sato, Y., and Rifkin, D. B. (1989) J. Cell. Biol., 109, 309–315.PubMedCrossRefGoogle Scholar
  116. 116.
    Mandriota, S. J., Menoud, P. A., and Pepper, M. S. (1996) J. Biol. Chem., 271, 11500–11505.PubMedCrossRefGoogle Scholar
  117. 117.
    Ramsauer, M., and D’Amore, P. A. (2002) J. Clin. Invest., 110, 1615–1617.PubMedGoogle Scholar
  118. 118.
    Ward, N. L., and Dumont, D. J. (2002) Semin. Cell Dev. Biol., 13, 19–27.PubMedCrossRefGoogle Scholar
  119. 119.
    Thurston, G. (2003) Cell Tissue Res., 314, 61–68.PubMedCrossRefGoogle Scholar
  120. 120.
    Suri, C., Jones, P. F., Patan, S., Bartunkova, S., Maisonpierre, P. C., Davis, S., Sato, T. N., and Yancopoulos, G. D. (1996) Cell, 87, 1171–1180.PubMedCrossRefGoogle Scholar
  121. 121.
    Sato, T. N., Tozawa, Y., Deutsch, U., Wolburg, B. K., Fujiwara, Y., Gendron, M. M., Gridley, T., Wolburg, H., Risau, W., and Qin, Y. (1995) Nature, 376, 70–74.PubMedCrossRefGoogle Scholar
  122. 122.
    Dumont, D. J., Gradwohl, G., Fong, G.-H., Puri, M. C., Gerstenstein, M., Auerbach, A., and Breitman, M. L. (1994) Genes Dev., 8, 1897–1909.PubMedCrossRefGoogle Scholar
  123. 123.
    Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T. H., Papadopoulos, N., Daly, T. J., Davis, S., Sato, T. N., and Yancopoulos, G. D. (1997) Science, 277, 55–60.PubMedCrossRefGoogle Scholar
  124. 124.
    Davis, S., Aldrich, T. H., Jones, P. F., Acheson, A., Compton, D. L., Jain, V., Ryan, T. E., Bruno, J., Radziejewski, C., Maisonpierre, P. C., and Yancopoulos, G. D. (1996) Cell, 87, 1161–1169.PubMedCrossRefGoogle Scholar
  125. 125.
    Witzenbichler, B., Maisonpierre, P. C., Jones, P., Yancopoulos, G. D., and Isner, J. M. (1998) J. Biol. Chem., 273, 18514–18521.PubMedCrossRefGoogle Scholar
  126. 126.
    Suri, C., McClain, J., Thurston, G., McDonald, D. M., Zhou, H., Oldmixon, E. H., Sato, T. N., and Yancopoulos, G. D. (1998) Science, 282, 468–471.PubMedCrossRefGoogle Scholar
  127. 127.
    Eklund, L., and Olsen, B. R. (2006) Exp. Cell Res., 312, 630–641.PubMedCrossRefGoogle Scholar
  128. 128.
    Holash, J., Wiegand, S. J., and Yancopoulos, G. D. (1999) Oncogene, 18, 5356–5362.PubMedCrossRefGoogle Scholar
  129. 129.
    Holash, J., Maisonpierre, P. C., Compton, D., Boland, P., Alexander, C. R., Zagzag, D., Yancopoulos, G. D., and Wiegand, S. J. (1999) Science, 284, 1994–1998.PubMedCrossRefGoogle Scholar
  130. 130.
    Stratmann, A., Risau, W., and Plate, K. H. (1998) Am. J. Pathol., 153, 1459–1466.PubMedGoogle Scholar
  131. 131.
    Carmeliet, P. (2005) Nature, 438, 932–936.PubMedCrossRefGoogle Scholar
  132. 132.
    Casanovas, O., Hicklin, D. J., Bergers, G., and Hanahan, D. (2005) Cancer Cell., 8, 299–309.PubMedCrossRefGoogle Scholar

Copyright information

© MAIK Nauka 2008

Authors and Affiliations

  1. 1.Institute of Carcinogenesis, Blokhin Cancer Research CenterRussian Academy of Medical SciencesMoscowRussia

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