Involvement of CTGF, a hypertrophic chondrocyte-specific gene product, in tumor angiogenesis

Connective tissue growth factor (CTGF) is a potent secreted signaling facto r which functions in multiple stages of angiogenesis. In the present study, we examined the role of CTGF in tumor angiogenesis and made the following observations: (1) Histological analysis of human breast cancer (MDA231) cel l and human fibrosarcoma (HT1080) cell xenografts in BALB/c nude mice showe d a high level of neovascularization. Human squamous cell carcinoma (A431) xenografts induced only a low level of neovascularization. (2) CTGF mRNA wa s strongly expressed in MDA231 and in HT1080 cells in vivo and in vitro, bu t not in A431 cells. (3) CTGF protein was markedly produced in MDA231 cells and HT1080 cells and secreted into culture medium, and its production was greater during phases of growth rather than confluency. (4) Production of C TGF in bovine aorta endothelial cells was induced by CTGF, VEGF, bFGF and T GF-beta. (5) Neovascularization induced by HT1080 cells or MDA231 cells on chicken chorioallantoic membrane was suppressed in the presence of neutrali zing CTGF-specific polyclonal antibody. These results suggest that CTGF reg ulates progression in tumor angiogenesis and the release or secretion of CT GF from tumor cells is essential for the angiogenesis. Copyright (C) 2001 S . Karger AG, Basel.