Mechanism on Androgen-unresponsive Cancer Cells in a Paracrine Growth Factor(s) Secreted from Shionogi Carcinoma 115 Cells Growth-stimulatory Effect of Androgen-induced Autocrine

Androgen-responsive (SC-3) and -unresponsive (SC-4) cloned cell lines in culture were established from an androgen-responsive mouse mammary tumor, Shionogi carcinoma 115. By using a serum-free medium [Hani's F-12:Kagle's minimum essential medium (1:1, v/v) containing 0.1% bo vine serum albumin), characteristics of androgen-induced and autonomous growth factors (GFs) were examined. Serum-free conditioned medium (CM) obtained from testosterone-stimulated (+T) SC-3 cells had re markable growth-stimulatory effects on both SC-3 and SC-4 cells. To examine the molecular characteristics of GF, CM(+T) from SC-3 was fractioned by heparin-Sepharose affinity chromatography; two peaks, eluted at 0.5 M (GF-low) and 1.1 M NaCI (GF-high) were identified. GFhigh had the ability to stimulate growth with a morphological change of both SC-3 and SC-4 cells; the GF-high was not found in CM from Tunstimulated (-T) SC-3 or CM from SC-4. GF-low stimulated the growth without the morphological change of only SC-4 cells; the GF-low was also present in CM(—T)from SC-3 and CM from SC-4. The present findings demonstrate that T-induced autocrine GF-high secreted from SC-3 cells can also stimulate the growth of progressed unresponsive SC4 cells in a paracrine mechanism and that autonomous GF-low secreted from both SC-3 and SC-4 cells can stimulate the growth of only SC-4 cells.