Density-dependent regulation of proliferation rate in cultured, androgen-responsive, tumour cells

Abstract

Short‐term cultures of androgen‐responsive Shionogi 115 (S115) cells exhibited density‐dependent regulation of proliferation rate in the presence or absence of testosterone. The average surface area per cell exposed to the growth medium was inversely proportional to population density. By contrast, long‐term cultures (serially passaged in testosterone‐containing medium for several months) did not exhibit density‐dependent regulation of proliferation rate when grown in testosterone‐containing medium. In this medium, cells became elongated and no longer exhibited any obvious decrease in exposed surface area with increasing density. Nevertheless, when subcultured into testosterone‐free medium, these cells reverted to an epithelial morphology and exhibited density‐dependent regulation of proliferation rate. These relationships suggested that the proliferation rate of cells decreased with density in proportion to the decrease in exposed surface area. Activity of the “A” neutral amino acid transport system decreased with density in proportion to the decrease in proliferation rate whereas activities of the “L” system and sugar transport system(s) did not. Treatment of cells with testosterone for 24 hours increased proliferation rate but did not change activity of the “A” system, indicating that activity of the “A” system changes with density but not with proliferation rate per se. It is suggested that a decrease in exposed surface area of cells produces the change in activity of the “A” system, possibly by changes in activity of the sodium pump.