The influence of mesenchyme of neonatal seminal vesicle and embryonic urogenital sinus on the morphologic and functional cytodifferentiation of dunning prostatic adenocarcinoma: Roles of growth factors and proto-oncogenes

Abstract

Previous studies have demonstrated that male genital tract mesenchymes can induce morphogenetic changes in the rat prostatic Dunning tumor (DT). However, the mechanism of these cellular interactions remains unknown. The aims of this paper are: (I) to examine the influence of neonatal seminal vesicle mesenchyme (SVM) and embryonic urogenital sinus mesenchyme (UGM) on the growth, and morphologic and functional cytodifferentiation of DT; (2) to investigate the possible role of growth factors and receptors including epidermal growth factor and its receptor, basic fibroblast growth factor and transforming growth factor-beta, and two proto-oncogenes, c-fos and c-jun, in these tumor-mesenchymal interactions. Combination of mesenchymes (SVM or UGM) with DT enhanced the growth and induced an apparently more normal morphologic cytodifferentiation in vivo with formation of large tubules lined by highly differentiated columnar epithelial cells and reappearance of fibromuscular stroma. The SDS-PAGE analysis has shown that the DT + UGM enlarged and small tubules secreted proteins different from those of parental DT, demonstrating that mesenchymes can also modulate the functional expression of DT. Interestingly, our immunohistochemical data demonstrate that all the selected growth factors, receptors, and proto-oncogenes are upregulated in the mesenchyme-induced DT epithelial cells, suggesting that these cellular regulators may be closely associated with the mesenchymal induction on the DT phenotypic changes in vivo. This finding implicates the potential role of these growth factors, receptors, and proto-oncogenes in the epigenetic pathway of prostate carcinogenesis via tumor-stromal interactions.