3 CELL-LINES SHOWING ANDROGEN-DEPENDENT, ANDROGEN-INDEPENDENT, AND ANDROGEN-SUPPRESSED PHENOTYPES, ESTABLISHED FROM A SINGLE TUMOR OF ANDROGEN-DEPENDENT SHIONOGI CARCINOMA-115

We investigated the heterogeneity of cells in terms of androgen responsiveness within a single tumor mass of Shionogi carcinoma SC-115 showing androgen-dependent growth. After cloning of the tumor by the limiting dilution method in the presence of androgen, we isolated 40 clones at random. Twenty-two clones required androgen for growth (androgen-dependent phenotype), 16 did not (androgen-independent phenotype), and the remaining two clones showed growth inhibition when androgen was added (androgen-suppressed phenotype). In addition, 22 androgen-dependent clones showed heterogeneity in growth factor sensitivity in the absence of androgen. All clones were sensitive to both acidic and basic fibroblast growth factor (FGF), 7 of 22 clones were sensitive to epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha, and 2 of 22 clones were sensitive to TGF-beta. This preexisting heterogeneity may be partly responsible for the growth of androgen-dependent tumor under hormone-deprived circumstances. Three typical clones, SC2G, SClG, and SC4A, were selected from androgen-dependent, -independent, and -suppressed phenotypic groups, respectively. These clones, as well as original solid tumors, were found to produce heparin-binding growth factors of heterogeneous elution positions. The molecular nature of these growth factors is not yet known. Neither anti-basic FGF antibody nor anti-EGF antibody inhibited the cell growth when added in cell culture, suggesting the factors were distinct from basic-FGF and EGF.