A novel snake venom disintegrin that inhibits human ovarian cancer dissemination and angiogenesis in an orthotopic nude mouse model.
OVCAR-5 is a human epithelial carcinoma cell line of the ovary, established from the ascitic fluid of a patient with progressive ovarian adenocarcinoma without prior cytotoxic treatment. The unique growth pattern of ovarian carcinoma makes it an ideal model for examining the anticancer activity of contortrostatin (CN), a homodimeric disintegrin from southern copperhead venom. FACS analysis revealed that OVCAR-5 is integrin alphavbeta3 negative, but alphavbeta5 positive. CN effectively blocks the adhesion of OVCAR-5 cells to several extracellular matrix proteins and inhibits tumor cell invasion through an artificial basement membrane. In a xenograft nude mouse model with intraperitoneal introduction of OVCAR-5 cells, intraperitoneal injection of CN was used for therapy. Tumor dissemination in CN-treated versus control groups was studied by gross examination, and antiangiogenic potential was examined by factor VIII immunohistochemistry and image analysis. CN not only significantly inhibited ovarian cancer dissemination in the nude mouse model, but it also dramatically prevented the recruitment of blood vessels to tumors at secondary sites.
Markland
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FS
Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA. markland@usc.edu
Shieh
K
K
Zhou
Q
Q
Golubkov
V
V
Sherwin
R P
RP
Richters
V
V
Sposto
R
R
D017836:Agkistrodon; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D019483:Disintegrins / Q000008:administration & dosage / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D012910:Snake Venoms / Q000737:chemistry*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation
D019483:Disintegrins; D016326:Extracellular Matrix Proteins; D012910:Snake Venoms; C403494:contortrostatin