Roles of growth factors in mediating mesenchymal influence on the cytodifferentiation of the dunning prostatic adenocarcinoma

Abstract

Earlier studies have shown that seminal vesicle mesenchyme (SVM) has the ability to induce Dunning tumor (Dr) to undergo morphogenetic changes and cytodifferentiation. The aim of the present study was to investigate the roles of growth factors and their receptors in tumor-mesenchymal interactions. Small pieces of DT were combined with SVM (O-day neonatal SD rat) and the tissue recombinants (SVM + DT) were grafted under the renal capsule of male athymic nude mice and allowed to grow for 4 weeks. Histopathological examination confirmed that SVM can induce DT to express apparently more normal morphological features, with the formation of large tubules lined by highly differentiated columnar epithelial cells and the reappearance of a fibromuscular stroma. Using immunohistochemistry, the results demonstrated that the tissue recombinants typically exhibited an overexpression of EGF, EGF-R, bFGF, TGF-β 1 together with a concurrent downregulation of TGF-α, IGF-I, IGF-II, and VEGF receptors (flk-1, fit-1). The levels of these growth factors and their receptors in DT + SVM tissue recombinants were more similar to those of the normal prostate. These findings reaffirmed that SVM has the ability to reprogram DT toward a more normal direction on one hand, while implicating the importance of cytokines in mesenchyme-induced DT phenotypic changes under in vivo condition on the other hand. This study suggests that these factors and their receptors may be essential mediators in tumor-mesenchymal interactions.