Carboxymethyl benzylamide dextran blocks angiogenesis of MDA-MB435 breast carcinoma xenografted in fat pad and its lung metastases in nude mice.

Abstract

We previously showed that carboxymethyl benzylamide dextran (CMDB7) prevents tumor growth and tumor angiogenesis by binding to angiogenic growth factors, thereby preventing them from reaching their receptors on tumor or stromal cells (Bagheri-Yarmand et al. Br. J. Cancer, 78: 111-118, 1998; Bagheri-Yarmand et al. Cell Growth Differ., 9: 497-504, 1998). In this study, CMDB7 inhibited neovessel formation within the fibroblast growth factor 2-enriched matrigel in mice, and its anticancer effect was then tested in a metastatic breast cancer model. Human MDA-MB435 cells were injected into the mammary fat pad of nude mice, and breast tumors developed within 1 week; all of the mice had lung metastases at 12 weeks. CMDB7 treatment (50, 150, or 300 s.c. or 300 i.v. mg/kg/week for 10 weeks) reduced the incidence of lung metastases to 12%. Histological analysis showed markedly less tumor neovascularization in the CMDB7-treated mice. Pulmonary metastasis incidence was strongly dependent on the intratumoral neoangiogenesis in primary tumors.