Sphingosine 1-phosphate and cell migration: resistance to angiogenesis inhibitors.
Naturally occurring angiogenesis inhibitors can inhibit different steps of the angiogenic process, such as endothelial cell migration. However, the mechanisms underlying this inhibition have not been elucidated. We demonstrate that migration of human umbilical vein endothelial cells induced by the potent endothelial cell chemoattractant sphingosine 1-phosphate is refractory to inhibition by well-characterized angiogenesis inhibitors such as endostatin and plasminogen-related protein-B. Our data support the contention that for effective blockage of tumor-induced angiogenesis, antagonists of both G protein-coupled receptor signaling and receptor tyrosine kinase signaling must be combined.
Morii
Takeshi
T
Orthopaedic Research Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Weissbach
Lawrence
L
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002465:Cell Movement; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D043169:Endostatins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008246:Lysophospholipids; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D010958:Plasminogen / Q000378:metabolism; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D008246:Lysophospholipids; C118420:PLGLB1 protein, human; C060506:sphingosine 1-phosphate; D010958:Plasminogen; D013110:Sphingosine