Influence of male genital tract mesenchymes on differentiation of Dunning prostatic adenocarcinoma

Abstract

Eighteen-day-old fetal urogenital sinus mesenchyme (UGM), 0-day-old neonatal seminal vesicle mesenchyme (SVM), 0-day-old neonatal bulbourethral gland mesenchyme (BUG-M), and 3-day-old neonatal urinary bladder mesenchyme (BLM) were isolated from rats and combined in vitro with 0.5-mm cubes of the R3327 androgen-dependent Dunning prostatic adenocarcinoma (DT). The resultant tissue combinations were grown as subcapsular renal grafts in male or female hosts. Grafts of the slow growing DT increased only marginally in size in male hosts and were composed of small tubules lined with an undifferentiated simple squamous to cuboidal epithelium. When grown in association with BLM the DT continued to exhibit its characteristic histodifferentiation and, based upon graft size, exhibited little growth in male hosts. By contrast, tissue combinations of UGM + DT, SVM + DT, and BUG-M + DT enlarged many-fold in size. DT carcinoma cells in combination with UGM, SVM, or BUG-M (a) were induced to undergo morphogenetic changes by forming larger more regularly organized ducts, (b) differentiated into a tall polarized columnar epithelial cells, and (c) produced secretion which accumulated in the lumen, when grown in male hosts. By DNA analysis, UGM + DT and SVM + DT combinations grown for 1 month were considerably larger than grafts of DT by itself and contained 1.76 and 1.97 times the amount of DNA than the sum of the individual components grown alone for 1 month in male hosts. Thus, the proliferative activity of DT cells appear to have been influenced by UGM and SVM. These findings show that the DT retains a responsiveness to its connective tissue environment which may alter certain aspects its pathobiology.