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

We previously showed that carboxymethyl benzylamide dextran (CMDB7) prevent s tumor growth and tumor angiogenesis by binding to angiogenic growth facto rs, thereby preventing them from reaching their receptors on tumor or strom al 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-enrich ed matrigel in mice, and its anticancer effect was then tested in a metasta tic breast cancer model. Human MDA-MB435 cells were injected into the mamma ry 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 met astases to 12%. Histological analysis showed markedly less tumor neovascula rization in the CMDB7-treated mice. Pulmonary metastasis incidence was stro ngly dependent on the intratumoral neoangiogenesis in primary tumors.