Growth stimulation of human breast cancer cells with anti-transforming growth factor beta antibodies: evidence for negative autocrine regulation by transforming growth factor beta

Abstrad ExogenousTGF$ inhibits the proliferation of human breast cancer cells in vitro. These cells synthesizeand secrete TGFft into their medium predominantly in a latent form. With neutralizing antibodies against native, biologically adive TGF� (278ab and 282ab), we have examined whether HS578T and MDA-231 breast cancer cells utilize their endogenousTGFft for growth regulation. Low levels of TGFfl adivity were detedable in conditioned medium from confluent monolayers of both cell lines in the absenceof acid or protease treatment as measured by radioreceptor assay.When added to subconfluent monolayersof the respectivecell line, this untreated conditioned medium inhibited DNA synthesis and cell proliferation. This inhibition was blocked by anti-TGFfl antibodies, whereas nonimmune rabbit IgG had no effed. Similar to exogenous TGF�1, this conditioned medium induced a dose-dependent increase in steady-state TGFfl1 mRNA levels when added to subconfluent HS578T cells; this increase was blocked by the 278ab. Consistent with the above, preincubation :� � � --+ +----++