Growth-Stimulating Effect of Growth Factor(s) from Androgen Independent Tumor Cells (CS 2-Cell) on Androgen Responsive Tumor Cells (SC 115-Cell)

Abstract

An androgen-responsive cloned cell line (SC U5-cell) from androgen-responsive Shionogi Carcinoma 115 (SC 115), and an androgen-independent cloned cell line (CS 2-cell) from an androgen-independent subline (CS 2) from SC U5 were established. When SC U5-cell and CS 2-cell were co-cultured in the serum-free medium, SC 115-cell grew similarly irrespective of the presence or absence of testosterone (T), although SC 115-cell alone did not proliferate without T. Conditioned medium (CM) from CS 2-cell cultured in the serum-free medium without T, stimulated growth of SC U5-cell and CS 2-cell. The CM showed proliferative activity on SC 115-cell and CS 2-cell in dose-dependent manner. When the concentrated CM was applied to a heparin Ultrogel column, the growth promoting activity was eluted at approximately 1.0 M NaCl. The activity of the partially purified CM was rather resistent to heat and acidic treatments, although it was lost by trypsin treatment. Effect of various growth factors on DNA sythesis of SC 115-cell was examined. Acidic fibroblast growth factor (FGF) stimulated DNA synthesis of SC 115-cell, and much greater effect was observed with basic FGF. The growth promotion rate of basic FGF was similar to that of the CM. Other growth factors examined did not show such stimulative activities. In conclusion, androgen-independent CS 2-cell secreted a growth promoting factor which controled the growth of CS 2-cell itself and also of parent SC 115-cell in autocrine or paracrine manner.