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Human cripto-1 (CR-1), a member of the Epidermal Growth Factor-Cripto FRL1 Crypitic (EGF-CFC) family, promotes cell proliferation and transformation of several mouse and human epithelial cell lines and is overexpressed in several human tumors. We investigated whether CR-1 also stimulates angiogenesis. Here we demonstrate for the first time that CR-1 stimulates proliferation, migration, invasion and differentiation into vascular-like structures on Matrigel of human umbilical endothelial cells (HUVEC). In vivo, recombinant CR-1 protein induces microvessel formation in Matrigel-filled silicone cylinders, and microvessel formation is statistically significantly inhibited with a blocking anti-CR-1 monoclonal antibody. Furthermore, tumors formed by CR-1-transfected MCF-7 cells in the cleared mammary fat pad of nude mice have higher microvessel density than tumors formed by control Neo-transfected MCF-7 cells. In conclusion, CR-1 appears to play an important role in the multistep process of angiogenesis.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]