Prostatic versus extraprostatic microenvironmental effects on growth and differentiation in the R-3327 prostatic adenocarcinoma model

No reliable method exists for accurately foretelling the biological outcome of prostatic carcinoma in humans. Inability to discriminate indolent from aggressive prostatic tumors relates to: 1) the absence of consistent, identifiable genetic lesions in malignant prostatic cancers and 2) an incomplete understanding of the influence of the prostatic microenvironment on tumor development and progression. We examined the in vivo growth and differentiation of Dunning R-3327 non-metastatic G and highly metastatic MAT-LyLu (MLL) prostatic adenocarcinoma sublines in prostatic vs extraprostatic microenvironments. Copenhagen male rats (30/group) received injections into the ventral prostate (i.p.), bulbocavernosus muscle (b.c.) or subcutis (s.c.) of 10⁴ MLL cells or 10⁵ G cells. The bulbocavernosus muscle contains androgen receptors and its growth is androgen regulated thus serving as an extraprostatic control tissue. Animals were sacrificed when s.c tumors reached 1 cm3 and tumors were weighed and processed for H&E staining. Tumors from G cells placed i.p. (n=30, 0 02 ± 0.04 g) were smaller (Wilcoxon, p < 0.001) than s.c. implants (n=30, 1.42 ± 1.02 g) and similar to the b.c. implants (n=29, 0.26 ± 0.34 g). Location did not affect tumor weight in MLL. Results indicate that androgen-responsive microenvironments regulate tumor growth in this model. The relatively indolent G tumor may respond to growth inhibitory signals present in the i.p. and b.c., which the aggressive MLL tumor may fail to recognize.