Modulations of breast fibroblast and carcinoma cell interactions by a dextran derivative (CMDB7)

Modulation of interactions between human breast carcinoma cells (MCF-7ras) and fibroblasts from normal breast tissue (MG3) and from a post-radiation fibrosis with recurrent breast carcinoma (FPR7) by a dextran derivative (CMDB7) was investigated. In a coculture system, MCF-7ras proliferation was increased (50%) by fibroblasts, and fibroblasts showed a 84% growth increase with MCF-7ras. This co-stimulation did not depend on fibroblast origin. CMDB7 can inhibit the growth of MCF-7ras but not the growth of fibroblasts. The addition of CMDB7 blocks the MCF-7ras stimulation by fibroblasts but not the fibroblast stimulation by MCF-7ras. Fibroblast-Conditioned Medium stimulated over 2-3 fold MCF-7ras's DNA synthesis but CMDB7 did not influence this paracrine stimulation. IGFI, IGFII stimulated MCF-7ras's DNA synthesis whereas bFGF inhibited it. CMDB7 did not block IGFI and IGFII's stimulatory effects but increased bFGF's inhibitory effects. These results indicate that CMDB7 can inhibit fibroblast-breast cancer cell interactions possibly by interfering with paracrine growth factor loops.