Change in morphological and functional cytodifferentiation induced by seminal vesicle mesenchyme in cell suspensions of rat Dunning prostatic adenocarcinoma cells.

Abstract

Previous experiments have shown that seminal vesicle mesenchyme (SVM) can induce small 0.5 mm fragments of the rat Dunning tumor (DT) to undergo secretory differentiation with a concomitant reduction in tumorigenesis. In the present experiments Dunning tumor epithelial cells (DTE) were purified from DT cell suspensions by Percoll gradient centrifugation and recombined with neonatal rat SVM. The resultant tissue recombinants (SVM + DTE) were grafted under the renal capsule of male athymic mice and grown for 2 months. Under these conditions SVM induced the DTE to exhibit a highly differentiated secretory phenotype by forming ducts lined with tall columnar epithelial cells or large clear cells with pale cytoplasm. Undifferentiated epithelial cells of the parental DT were rarely observed in these tissue recombinants. The loss of tumorigenicity in SVM + DTE recombinants was associated with a striking reduction of epithelial 3H-thymidine labeling index in SVM + DTE recombinants (DT = 8.31%; SVM + DTE recombinants = 1.10%). Differences in putative secretory proteins were also observed by SDS-PAGE in SVM + DTE recombinants in comparison with DT. Testosterone metabolism was examined in epithelial cells recovered from grafts of DT vs. SVM + DTE tissue recombinants by thin layer chromatography and revealed that the major metabolite produced by DTE was androstenedione, whereas in epithelium isolated from SVM + DTE tissue recombinants the major androgen metabolite was 5alpha-DHT. Thus, after induction by SVM the DTE metabolized androgens in a pattern similar to the normal rat dorsal prostate. The SVM-induced changes in DTE suggest the possibility that emerging or established carcinomas might be regulated at least in part by their connective tissue microenvironment.