Castration‐induced changes in morphology, androgen levels, and proliferative activity of human prostate cancer tissue grown in athymic nude mice

Abstract

The transplantable human prostate tumor lines PC-82 and PC-EW regress after androgen depletion. The castration-induced decline in tumor volume was faster in the PC-EW tumor (half-life 6 days) than in the PC-82 tumor (half-life 18 days), despite similar castrate androgen levels of less than 3 pmol/g tissue. Androgen ablation of the PC-82 tumor induced a wave of apoptosis, whereas in the PC-EW tumor, necrotic cell death was predominantly observed. The proliferative activity (BrdU index) of PC-82 and PC-EW tumor tissue declined from 3% to less than 1% after castration. After androgen depletion, some proliferative activity remained, the major part of which was localized in the (murine) stromal compartment of the tumors. In contrast to the PC-EW tumors, regrowth of androgen-ablated PC-82 tumors was rapidly induced by androgen resubstitution. The differences in response of these tumor models to androgen depletion and repletion appear to be related to the putative involvement of different cell death pathways. The role of the stroma in these processes is unclear.

Short-term cellular effects induced by castration therapy in relation to clinical outcome in prostate cancer

“…Together with our earlier results (Westin et al, 1995a), these data may reconcile contradictory data from experimental models; for instance, castration induced an increase in apoptotic rate, a decrease in proliferation rate and caused severe morphological destruction in PC-82 human prostate cancer grown in nude mice (Kyprianou et al, 1990;van Werden et al, 1993). Implants of the newly established LuCaP 23.1 tumour cell line grown in nude mice also underwent an increase in apoptosis and a decrease in proliferation after castration (Bladou et al, 1996).…”

Human prostate cancer heterotransplants: a review on this experimental model

“…Therefore, the heterotransplanted tumor, in the first passage, always showed a histopathological pattern typical of human prostate carcinoma. This fidelity has been demonstrated for well-differentiated, moderately differentiated and poorly differentiated carcinomas, as well as metastatic tumors that are moderately to poorly differentiated [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Similar results were obtained with poorly differentiated primary carcinomas when the implantation site was the renal subcapsule [29].…”

Dietary n-3 Polyunsaturated Fatty Acids Enhance Hormone Ablation Therapy in Androgen-Dependent Prostate Cancer

“…33,34 Apoptotic cells in xenograft tumors stained for cleaved caspase-3 by immunohistochemistry but this technique did not improve sensitivity or specificity (not shown).…”