Endothelial survival factors as targets for antineoplastic therapy.
Angiogenesis is essential for the growth and metastasis of solid tumors. The angiogenic process includes not only development of new blood vessels but also maintenance of the existing vasculature. Recent studies have demonstrated that several factors induce angiogenesis and also function as endothelial cell survival factors. Vascular endothelial growth factor, a potent angiogenic factor, is an endothelial cell survival factor whose tyrosine kinase receptors are limited to endothelial cells. Members of the angiopoietin family also bind to an endothelial cell-specific tyrosine kinase receptor. Angiopoietin-1 has been shown to stabilize endothelial cell networks, whereas angiopoietin-2 is antagonistic to angiopoietin-1 and destabilizes endothelial cell networks. Pericytes contribute to endothelial cell stabilization by cell-cell contact, secretion of survival factors, or both. In addition, integrins may function as endothelial cell survival factors by numerous mechanisms after binding to the extracellular matrix. The effects of many endothelial cell survival factors act in concert with vascular endothelial growth factor to enhance this essential step in angiogenesis. Targeting any of the aforementioned mechanisms for endothelial cell survival may provide novel therapeutic antineoplastic strategies.
Reinmuth
N
N
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Stoeltzing
O
O
Liu
W
W
Ahmad
S A
SA
Jung
Y D
YD
Fan
F
F
Parikh
A
A
Ellis
L M
LM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D042683:Angiopoietin-1; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002470:Cell Survival; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D016023:Integrins / Q000378:metabolism; D008222:Lymphokines / Q000037:antagonists & inhibitors*; D008562:Membrane Glycoproteins / Q000627:therapeutic use; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000078183:Oxindoles; D020286:Pericytes / Q000378:metabolism; D011422:Propionates; D011758:Pyrroles / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D042787:Receptor, TIE-2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D007211:Indoles; D016023:Integrins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C116890:Semaxinib; C412603:orantinib; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2