PARACRINE INTERACTION IN COCULTURE 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-depen dent (MCF-7, ZR75.1) and hormone-independent (MDAMB-231, BT20) breast cancer cell lines. Both hormone-independent cell lines were able to st imulate the growth of the hormone-dependent lines, whereas the opposit e 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 gr owth factor alpha (TGFalpha) or insulin-like growth factor I (IGF-1). Similarly, treatment with a neutralizing anti TGFalpha antibody impair ed the growth stimulation exerted by hormone-independent cells on horm one-dependent cells. These results confirm the important role of parac rine interactions in control of the growth of human heterogeneous brea st tumors and suggest that the main growth factors involved in such in teractions are TGFalpha and probably some growth factors from the insu lin-like growth factor family rather than IGF-I itself.