Growth factor interactions between mouse mammary cell lines cocultured in collagen gels

Three related mouse mammary cell lines were cultured in collagen gels and assayed for growth factor responsiveness and interaction via soluble factors. The CL-S1 cell line is nontumorigenic and grows poorly in collagen gel culture. The +SA and -SA cell lines exhibit different degrees of malignant behavior in vivo and have different growth properties in vitro. In collagen gel culture, +SA growth was stimulated by serum but not by epidermal growth factor (EGF), whereas both serum and EGF were required for optimal growth of -SA cells of early passage number as well as CL-S1 cells. -SA cells of later passage repeatedly exhibited a change so as to no longer require serum while retaining EGF responsiveness. [125I]EGF binding analyses indicated that CL-S1 cells bound EGF with less affinity than did -SA cells whereas +SA cells bound almost no ligand. When cell lines were maintained in separate collagen gels but shared the same culture medium, growth of +SA or -SA cells was slightly enhanced in the presence of CL-S1 cells and -SA cell growth was enhanced by the presence of +SA cells. Using the normal rat kidney fibroblast line NRK (clone 49F) as an indicator, serum-containing conditioned media from each cell line and from each pair of cell lines cultured in collagen gels were tested for transforming growth factor (TGF) activity. Both the -SA and CL-S1 lines tested positive for TGF-alpha production and possibly released a TGF-beta activity. These results suggest mechanisms by which cell populations in and around tumors can modify one another's growth characteristics.