Advertisement

Signalling Pathways and Adhesion Molecules as Targets for Antiangiogenesis Therapy in Tumors

  • Gianfranco Bazzoni
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 610)

In the embryo, blood vessels derive from endothelial precursors in a process called vasculogenesis. These progenitors assemble into a primitive vascular plexus. Subsequently, in a process called angiogenesis, the primitive vascular plexus expands by means of vessel sprouting and organizes into a network of blood vessels. Finally, the developing vessels are reinforced by the association with pericytes and smooth muscle cells (Coultas, et al. 2005). In parallel, in a process called lymphangiogenesis, lymphatic endothelial cells, which derive from embryonic veins by sprouting, form primary lymph sacs and the primary lymphatic plexus (Alitalo and Carmeliet 2002).

Keywords

Vascular Endothelial Growth Factor Adherens Junction Embryonic Lethality Vascular Development Lymphatic Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Achen, M. G.; B. K. McColl and S. A. Stacker (2005). Focus on lymphangiogenesis in tumor metastasis. Cancer Cell 7: 121–7.PubMedCrossRefGoogle Scholar
  2. Alitalo, K. and P. Carmeliet (2002). Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 1: 219–27.PubMedCrossRefGoogle Scholar
  3. Alitalo, K.; T. Tammela and T. V. Petrova (2005). Lymphangiogenesis in development and human disease. Nature 438: 946–53.PubMedCrossRefGoogle Scholar
  4. Bader, B. L.; H. Rayburn; D. Crowley and R. O. Hynes (1998). Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins. Cell 95: 507–19.PubMedCrossRefGoogle Scholar
  5. Bazzoni, G. (2003). The JAM family of junctional adhesion molecules. Curr Opin Cell Biol 15: 525–30.PubMedCrossRefGoogle Scholar
  6. Bazzoni, G. and E. Dejana (2004). Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84: 869–901.PubMedCrossRefGoogle Scholar
  7. Bazzoni, G., E. Dejana and M. G. Lampugnani (1999). Endothelial adhesion molecules in the development of the vascular tree: the garden of forking paths. Curr Opin Cell Biol 11: 573–81.PubMedCrossRefGoogle Scholar
  8. Cambier, S.; S. Gline; D. Mu; R. Collins; J. Araya; G. Dolganov; S. Einheber; N. Boudreau and S. L. Nishimura (2005). Integrin alpha(v) beta8-mediated activation of transforming growth factor-beta by perivascular astrocytes: an angiogenic control switch. Am J Pathol 166: 1883–94.PubMedGoogle Scholar
  9. Carmeliet, P. (2005). Angiogenesis in life, disease and medicine. Nature 438: 932–6.PubMedCrossRefGoogle Scholar
  10. Carmeliet, P.; M. G. Lampugnani; L. Moons; F. Breviario; V. Compernolle; F. Bono; G. Balconi; R. Spagnuolo; B. Oostuyse; M. Dewerchin; A. Zanetti; A. Angellilo; V. Mattot; D. Nuyens; E. Lutgens; F. Clotman; M. C. de Ruiter; A. Gittenberger-de Groot; R. Poelmann; F. Lupu; J. M. Herbert; D. Collen and E. Dejana (1999). Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 98: 147–57.PubMedCrossRefGoogle Scholar
  11. Carmeliet, P. and M. Tessier-Lavigne (2005). Common mechanisms of nerve and blood vessel wiring. Nature 436: 193–200.PubMedCrossRefGoogle Scholar
  12. Cattelino, A.; S. Liebner; R. Gallini; A. Zanetti; G. Balconi; A. Corsi; P. Bianco; H. Wolburg; R. Moore; B. Oreda; R. Kemler and E. Dejana (2003). The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility. J Cell Biol 162: 1111–22.PubMedCrossRefGoogle Scholar
  13. Cavallaro, U.; S. Liebner and E. Dejana (2006). Endothelial cadherins and tumor angiogenesis. Exp Cell Res 312: 659–67.PubMedCrossRefGoogle Scholar
  14. Cera, M. R.; A. Del Prete; A. Vecchi; M. Corada; I. Martin-Padura; T. Motoike; P. Tonetti; G. Bazzoni; W. Vermi; F. Gentili; S. Bernasconi; T. N. Sato A. Mantovani and E. Dejana (2004). Increased DC trafficking to lymph nodes and contact hypersensitivity in junctional adhesion molecule-A-deficient mice. J Clin Invest 114: 729–38.PubMedGoogle Scholar
  15. Corada, M.; F. Liao; M. Lindgren; M. G. Lampugnani; F. Breviario; R. Frank; W. A. Muller; D. J. Hicklin P. Bohlen and E. Dejana (2001). Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability. Blood 97: 1679–84.PubMedCrossRefGoogle Scholar
  16. Coultas, L., K. Chawengsaksophak and J. Rossant (2005). Endothelial cells and VEGF in vascular development. Nature 438: 937–45.PubMedCrossRefGoogle Scholar
  17. Dejana, E. (2004). Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol 5: 261–70.PubMedCrossRefGoogle Scholar
  18. Dumont, D. J.; L. Jussila; J. Taipale; A. Lymboussaki; T. Mustonen; K. Pajusola M. Breitman and K. Alitalo (1998). Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science 282: 946–9.PubMedCrossRefGoogle Scholar
  19. Fassler, R. and M. Meyer (1995). Consequences of lack of beta 1 integrin gene expression in mice. Genes Dev 9: 1896–908.PubMedCrossRefGoogle Scholar
  20. Ferrara, N. and R. S. Kerbel (2005). Angiogenesis as a therapeutic target. Nature 438: 967–74.PubMedCrossRefGoogle Scholar
  21. Fong, G. H.; J. Rossant; M. Gertsenstein and M. L. Breitman (1995). Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376: 66–70.PubMedCrossRefGoogle Scholar
  22. Francis, S. E.; K. L. Goh; K. Hodivala-Dilke; B. L. Bader; M. Stark D. Davidson and R. O. Hynes (2002). Central roles of alpha5beta1 integrin and fibronectin in vascular development in mouse embryos and embryoid bodies. Arterioscler Thromb Vasc Biol 22: 927–33.PubMedCrossRefGoogle Scholar
  23. Gerhardt, H.; M. Golding; M. Fruttiger; C. Ruhrberg; A. Lundkvist; A. Abramsson; M. Jeltsch; C. Mitchell; K. Alitalo, D. Shima and C. Betsholtz (2003). VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161: 1163–77.PubMedCrossRefGoogle Scholar
  24. Hiratsuka, S.; O. Minowa; J. Kuno T. Noda and M. Shibuya (1998). Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice. Proc Natl Acad Sci U S A 95: 9349–54.PubMedCrossRefGoogle Scholar
  25. Hodivala-Dilke, K. M.; K. P. McHugh; D. A. Tsakiris; H. Rayburn; D. Crowley; M. Ullman-Cullere; F. P. Ross; B. S. Coller; S. Teitelbaum and R. O. Hynes (1999). Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest 103: 229–38.PubMedCrossRefGoogle Scholar
  26. Hurwitz, H., 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 and F. Kabbinavar (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335–42.PubMedCrossRefGoogle Scholar
  27. Hynes, R. O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110: 673–87.PubMedCrossRefGoogle Scholar
  28. Karkkainen, M. J.; P. Haiko; K. Sainio; J. Partanen; J. Taipale; T. V. Petrova; M. Jeltsch; D. G. Jackson; M. Talikka; H. Rauvala; C. Betsholtz and K. Alitalo (2004). Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 5: 74–80.PubMedCrossRefGoogle Scholar
  29. Karpanen, T.; M. Egeblad; M. J. Karkkainen; H. Kubo; S. Yla-Herttuala; M. Jaattela and K. Alitalo (2001). Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res 61: 1786–90.PubMedGoogle Scholar
  30. Lampugnani, M. G.; A. Zanetti; M. Corada; T. Takahashi; G. Balconi; F. Breviario; F. Orsenigo; A. Cattelino; R. Kemler T. O. Daniel and E. Dejana (2003). Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. J Cell Biol 161: 793–804.CrossRefGoogle Scholar
  31. Liebner, S.; A. Cattelino; R. Gallini; N. Rudini; M. Iurlaro; S. Piccolo and E. Dejana (2004). Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J Cell Biol 166: 359–67.PubMedCrossRefGoogle Scholar
  32. Lindahl, P.; B. R. Johansson; P. Leveen and C. Betsholtz (1997). Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277: 242–5.PubMedCrossRefGoogle Scholar
  33. Lyden, D.; 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. Hajjar; K. Manova; R. Benezra and S. Rafii (2001). Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7: 1194–201.PubMedCrossRefGoogle Scholar
  34. Maeshima, Y.; A. Sudhakar; J. C. Lively; K. Ueki; S. Kharbanda; C. R. Kahn; N. Sonenberg; R. O. Hynes and R. Kalluri (2002). Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. Science 295: 140–3.PubMedCrossRefGoogle Scholar
  35. Maisonpierre, P. C.; C. Suri; P. F. Jones; S. Bartunkova; S. J. Wiegand; C. Radziejewski; D. Compton; J. McClain; T. H. Aldrich; N. Papadopoulos; T. J. Daly; S. Davis; T. N. Sato and G. D. Yancopoulos (1997). Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277: 55–60.PubMedCrossRefGoogle Scholar
  36. McCarty, J. H.; R. A. Monahan-Earley; L. F. Brown; M. Keller; H. Gerhardt; K. Rubin; M. Shani; H. F. Dvorak; H. Wolburg; B. L. Bader A. M. Dvorak and R. O. Hynes (2002). Defective associations between blood vessels and brain parenchyma lead to cerebral hemorrhage in mice lacking alphav integrins. Mol Cell Biol 22: 7667–77.PubMedCrossRefGoogle Scholar
  37. Nikolopoulos, S. N.; P. Blaikie; T. Yoshioka; W. Guo and F. G. Giancotti (2004). Integrin beta4 signaling promotes tumor angiogenesis. Cancer Cell 6: 471–83.PubMedCrossRefGoogle Scholar
  38. Nitta, T.; M. Hata; S. Gotoh; Y. Seo; H. Sasaki; N. Hashimoto; M. Furuse and S. Tsukita (2003). Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 161: 653–60.PubMedCrossRefGoogle Scholar
  39. O’Reilly, M. S.; T. Boehm; Y. Shing; N. Fukai; G. Vasios; W. S. Lane; E. Flynn; J. R. Birkhead; B. R. Olsen and J. Folkman (1997). Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88: 277–85.PubMedCrossRefGoogle Scholar
  40. Oliner, J.; H. Min; J. Leal; D. Yu; S. Rao; E. You; X. Tang; H. Kim; S. Meyer; S. J. Han; N. Hawkins; R. Rosenfeld; E. Davy; K. Graham; F. Jacobsen; S. Stevenson; J. Ho; Q. Chen; T. Hartmann; M. Michaels; M. Kelley; L. Li; K. Sitney; F. Martin; J. R. Sun; N. Zhang; J. Lu; J. Estrada; R. Kumar; A. Coxon; S. Kaufman; J. Pretorius; S. Scully; R. Cattley; M. Payton; S. Coats; L. Nguyen; B. Desilva; A. Ndifor; I. Hayward; R. Radinsky, T. Boone and R. Kendall (2004). Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2. Cancer Cell 6: 507–16.PubMedCrossRefGoogle Scholar
  41. Pasquale, E. B. (2005). Eph receptor signalling casts a wide net on cell behavior. Nat Rev Mol Cell Biol 6: 462–75.PubMedCrossRefGoogle Scholar
  42. Pike, S. E.; L. Yao; K. D. Jones; B. Cherney; E. Appella; K. Sakaguchi; H. Nakhasi; J. Teruya-Feldstein; P. Wirth; G. Gupta and G. Tosato (1998). Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth. J Exp Med 188: 2349–56.PubMedCrossRefGoogle Scholar
  43. Reynolds, L. E.; L. Wyder; J. C. Lively; D. Taverna; S. D. Robinson; X. Huang; D. Sheppard R. O. Hynes and K. M. Hodivala-Dilke (2002). Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 8: 27–34.PubMedCrossRefGoogle Scholar
  44. Saitou, M.; M. Furuse; H. Sasaki; J. D. Schulzke; M. Fromm; H. Takano; T. Noda and S. Tsukita (2000). Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11: 4131–42.PubMedGoogle Scholar
  45. Serini, G.; D. Valdembri and F. Bussolino (2006). Integrins and angiogenesis: a sticky business. Exp Cell Res 312: 651–8.PubMedCrossRefGoogle Scholar
  46. Shalaby, F.; J. Rossant; T. P. Yamaguchi; M. Gertsenstein; X. F. Wu; M. L. Breitman and A. C. Schuh (1995). Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376: 62–6.PubMedCrossRefGoogle Scholar
  47. Shibuya, M. and L. Claesson-Welsh (2006). Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res 312: 549–60.PubMedCrossRefGoogle Scholar
  48. Silvestre, J. S.; C. Thery, G. Hamard; J. Boddaert; B. Aguilar; A. Delcayre; C. Houbron; R. Tamarat; O. Blanc-Brude; S. Heeneman; M. Clergue; M. Duriez; R. Merval; B. Levy; A. Tedgui; S. Amigorena and Z. Mallat (2005). Lactadherin promotes VEGF-dependent neovascularization. Nat Med 11: 499–506.PubMedCrossRefGoogle Scholar
  49. Soldi, R.; S. Mitola; M. Strasly; P. Defilippi; G. Tarone and F. Bussolino (1999). Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. Embo J 18: 882–92.PubMedCrossRefGoogle Scholar
  50. Stacker, S. A.; C. Caesar; M. E. Baldwin; G. E. Thornton; R. A. Williams; R. Prevo; D. G. Jackson; S. Nishikawa; H. Kubo and M. G. Achen (2001). VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med 7: 186–91.PubMedCrossRefGoogle Scholar
  51. Stephens, L. E.; A. E. Sutherland; I. V. Klimanskaya; A. Andrieux; J. Meneses R. A. Pedersen and C. H. Damsky (1995). Deletion of beta 1 integrins in mice results in inner cell mass failure and peri-implantation lethality. Genes Dev 9: 1883–95.PubMedCrossRefGoogle Scholar
  52. Stupack, D. G.; X. S. Puente; S. Boutsaboualoy C. M. Storgard and D. A. Cheresh (2001). Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins. J Cell Biol 155: 459–70.PubMedCrossRefGoogle Scholar
  53. Sund, M.; Y. Hamano; H. Sugimoto; A. Sudhakar; M. Soubasakos; U. Yerramalla; L. E. Benjamin; J. Lawler; M. Kieran A. Shah and R. Kalluri (2005). Function of endogenous inhibitors of angiogenesis as endothelium-specific tumor suppressors. Proc Natl Acad Sci U S A 102: 2934–9.PubMedCrossRefGoogle Scholar
  54. Suri, C.; P. F. Jones; S. Patan; S. Bartunkova; P. C. Maisonpierre; S. Davis T. N. Sato and G. D. Yancopoulos (1996). Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87: 1171–80.PubMedCrossRefGoogle Scholar
  55. Takahashi, T., H. Ueno and M. Shibuya (1999). VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene 18: 2221–30.PubMedCrossRefGoogle Scholar
  56. Tucker, G. C. (2003). Alpha v integrin inhibitors and cancer therapy. Curr Opin Investig Drugs 4: 722–31.PubMedGoogle Scholar
  57. van der Neut, R.; P. Krimpenfort; J. Calafat, C. M. Niessen and A. Sonnenberg (1996). Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice. Nat Genet 13: 366–9.PubMedCrossRefGoogle Scholar
  58. Wallez, Y., I. Vilgrain and P. Huber (2006). Angiogenesis: the VE-cadherin switch. Trends Cardiovasc Med 16: 55–9.PubMedCrossRefGoogle Scholar
  59. Watanabe, K.; Y. Hasegawa; H. Yamashita; K. Shimizu; Y. Ding; M. Abe; H. Ohta; K. Imagawa; K. Hojo; H. Maki, H. Sonoda and Y. Sato (2004). Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis. J Clin Invest 114: 898–907.PubMedGoogle Scholar
  60. Yancopoulos, G. D.; S. Davis; N. W. Gale; J. S. Rudge; S. J. Wiegand and J. Holash (2000). Vascular-specific growth factors and blood vessel formation. Nature 407: 242–8.PubMedCrossRefGoogle Scholar
  61. Yang, J. T.; H. Rayburn and R. O. Hynes (1993). Embryonic mesodermal defects in alpha 5 integrin-deficient mice. Development 119: 1093–105.PubMedGoogle Scholar
  62. Zakarija, A. and G. Soff (2005). Update on angiogenesis inhibitors. Curr Opin Oncol 17: 578–83.PubMedCrossRefGoogle Scholar
  63. Zhu, J.; K. Motejlek; D. Wang; K. Zang, A. Schmidt and L. F. Reichardt (2002). beta8 integrins are required for vascular morphogenesis in mouse embryos. Development 129: 2891–903.PubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Gianfranco Bazzoni
    • 1
  1. 1.Department of Biochemistry and Molecular PharmacologyIstituto di Ricerche Farmacologiche Mario NegriMilanoItaly

Personalised recommendations