Mesenchyme-induced changes in the neoplastic characteristics of the Dunning prostatic adenocarcinoma

To investigate the possibility that mesenchyme can alter the neoplastic properties of an established carcinoma, small (0.5-mm cubes) pieces of the Dunning prostatic adenocarcinoma (DT) were grown in association with seminal vesicle mesenchyme (SVM) for 1 mo. Differentiated DT epithelial cells harvested from the resultant tissue recombinants (1 degree SVM + DT) were recombined with fresh SVM to generate 2 degrees SVM + DT recombinants which were grafted to secondary male hosts. After 3 additional mo of in vivo growth, grafts of (a) 2 degrees SVM + DT recombinants, (b) DT epithelial cells derived from 1 degree SVM + DT recombinants, or (c) DT by itself were examined for growth rate and tumorigenicity. Grafts of DT by itself formed large tumorous masses that completely overgrew the host's kidney, while 2 degrees SVM + DT recombinants and differentiated DT epithelial cells from 1 degree SVM + DT recombinants exhibited only modest growth during a 3-mo period. The loss of tumorigenicity was associated with a striking reduction in [3H]thymidine labeling index in epithelial cells of 2 degrees SVM + DT recombinants. DT grafted by itself maintained its typical histopathological characteristics containing small ducts lined with undifferentiated squamous to cuboidal epithelial cells. Grafts of 2 degrees SVM + DT recombinants contained large ducts lined by epithelial cells exhibiting three different patterns of histodifferentiation: (a) basophilic tall columnar epithelial cells with a clear supranuclear cytoplasm and basally located oval nuclei; (b) a heterogeneous epithelium containing large clear cells with pale cytoplasm interspersed among dark staining tall columnar epithelial cells; and (c) undifferentiated squamous to cuboidal epithelial cells. The first two epithelial types were the predominant cell types. Grafts of differentiated DT epithelial cells derived from 1 degree SVM + DT recombinants formed medium-sized ducts lined with cuboidal to low columnar epithelial cells. These results demonstrate a continued responsiveness of carcinoma cells to mesenchymal inductors which can induce secretory cytodifferentiation and elicit a reduction in growth rate and loss of tumorigenesis.