Laminin binding to the calreticulin fragment vasostatin regulates endothelial cell function.
Vasostatin, the 1-180 amino acids NH(2) domain of calreticulin, inhibits endothelial cell proliferation, angiogenesis, and tumor growth, but the mechanisms underlying these effects are unclear. We show that endothelial cells express the extracellular matrix protein laminin, including chains alpha 5 and gamma 1 and that vasostatin specifically binds to laminin. When added to endothelial cell cultures, vasostatin specifically inhibits endothelial cell attachment to laminin and by this mechanism, can reduce subsequent endothelial cell growth induced by basic fibroblast growth factor. As an angiogenesis inhibitor that specifically disrupts endothelial cell attachment to components of the extracellular matrix, vasostatin has a unique potential as a cancer therapeutic.
Yao
Lei
L
Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. yaol@mail.nih.gov
Pike
Sandra E
SE
Tosato
Giovanna
G
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002135:Calcium-Binding Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D037282:Calreticulin; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D007797:Laminin / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D012261:Ribonucleoproteins / Q000494:pharmacology* / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D016326:Extracellular Matrix Proteins; D007797:Laminin; D010446:Peptide Fragments; D012261:Ribonucleoproteins; C121986:vasostatin