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Growth-stimulatory Effect of Androgen-induced Autocrine Growth Factor(s) Secreted from Shionogi Carcinoma 115 Cells on Androgen-unresponsive Cancer Cells in a Paracrine Mechanism¹

Departments of Pathology [N. Na., K. M.], Internal Medicine [B. S.], and Urology [N. No., T. S.], Osaka University Medical School, Kita-ku, Osaka 530; Shionogi Research Laboratory, Fukushima-ku, Osaka 553 [N. U.]; and Department of Surgery, The Center for Adult Diseases, Higashinari-ku, Osaka 537 [S. N.], Japan

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 [Ham's F-12:Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine 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 remarkable 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 NaCl (GF-high) were identified. GF-high 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 T-unstimulated (-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 SC-4 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.

¹ Supported in part by a grant-in-aid for Cancer Research from the Ministry of Education, Science and Culture.

² To whom requests for reprints should be addressed.

Received 3/ 3/88. Revised 5/27/88. Accepted 6/ 3/88.

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