CYR61, a product of a growth factor-inducible immediate early gene, promotes angiogenesis and tumor growth.
CYR61 is a secreted, cysteine-rich, heparin-binding protein encoded by a growth factor-inducible immediate-early gene. Acting as an extracellular, matrix-associated signaling molecule, CYR61 promotes the adhesion of endothelial cells through interaction with the integrin alphaVbeta3 and augments growth factor-induced DNA synthesis in the same cell type. In this study, we show that purified CYR61 stimulates directed migration of human microvascular endothelial cells in culture through an alphaV beta3-dependent pathway and induces neovascularization in rat corneas. Both the chemotactic and angiogenic activities of CYR61 can be blocked by specific anti-CYR61 antibodies. Whereas most human tumor-derived cell lines tested express CYR61, the gastric adenocarcinoma cell line RF-1 does not. Expression of the CYR61 cDNA under the regulation of a constitutive promoter in RF-1 cells significantly enhances the tumorigenicity of these cells as measured by growth in immunodeficient mice, resulting in tumors that are larger and more vascularized than those produced by control RF-1 cells. Taken together, these results identify CYR61 as an angiogenic inducer that can promote tumor growth and vascularization; the results also suggest potential roles for CYR61 in physiologic and pathologic neovascularization.
Babic
A M
AM
Department of Molecular Genetics, M/C 669, University of Illinois at Chicago College of Medicine, 900 South Ashland Avenue, Chicago, IL 60607-7170, USA.
Kireeva
M L
ML
Kolesnikova
T V
TV
Lau
L F
LF
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects; D055515:Cysteine-Rich Protein 61; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D014407:Tumor Cells, Cultured
C501848:CCN1 protein, human; C491850:CCN1 protein, mouse; C501849:CCN1 protein, rat; D055515:Cysteine-Rich Protein 61; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins