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

Earlier studies have shown that seminal vesicle mesenchyme (SVM) has the ab ility to induce Dunning tumor (DT) to undergo morphogenetic changes and cyt odifferentiation. The aim of the present study was to investigate the roles of growth factors and their receptors in tumor-mesenchymal interactions. S mall pieces of DT were combined with SVM (0-day neonatal SD rat) and the ti ssue recombinants (SVM + DT) were grafted under the renal capsule of male a thymic nude mice and allowed to grow for 4 weeks. Histopathological examina tion confirmed that SVM can induce DT to express apparently more normal mor phological features, with the formation of large tubules lined by highly di fferentiated columnar epithelial cells and the reappearance of a fibromuscu lar stroma. Using immunohistochemistry, the results demonstrated that the t issue recombinants typically exhibited an overexpression of EGF, EGF-R, bFG F, TGF-beta(1) together with a concurrent downregulation of TGF-alpha, IGF- I, IGF-II, and VEGF receptors (flk-1, flt-1). The levels of these growth fa ctors and their receptors in DT + SVM tissue recombinants were more similar to those of the normal prostate. These findings reaffirmed that SVM has th e ability to reprogram DT toward a more normal direction on one hand, while implicating the importance of cytokines in mesenchyme-induced DT phenotypi c changes under in vivo condition on the other hand. This study suggests th at these factors and their receptors may be essential mediators in tumor-me senchymal interactions. Copyright (C) 2000 S. Karger AG, Basel.