Paracrine interaction in co-culture of hormone-dependent and independent breast cancer cells.

A permeable solid support (Transwell Coll.) was used to develop serum-free co-cultures allowing paracrine interactions between hormone-dependent (MCF-7, ZR75.1) and hormone-independent (MDAMB-231, BT20) breast cancer cell lines. Both hormone-independent cell lines were able to stimulate the growth of the hormone-dependent lines, whereas the opposite was observed only in the case of BT20 co-culture with ZR75.1 cells. The cell growth stimulation observed in co-cultures could be abolished by the addition to the culture medium of an excess of transforming growth factor alpha (TGF alpha) or insulin-like growth factor I (IGF-I). Similarly, treatment with a neutralizing anti TGF alpha antibody impaired the growth stimulation exerted by hormone-independent cells on hormone-dependent cells. These results confirm the important role of paracrine interactions in control of the growth of human heterogeneous breast tumors and suggest that the main growth factors involved in such interactions are TGF alpha and probably some growth factors from the insulin-like growth factor family rather than IGF-I itself.