title: Stromal-epithelial paracrine interactions in the neoplastic rat and human prostate.
abstract: Homotypic paracrine interactions in the rat and human prostate have been investigated using prostatic stromal cells and neoplastic epithelial cells (PA-III, rat; TSU-pr1, human). Secretory proteins prepared from each cell type were used to determine the dose dependent regulation of growth (DNA synthesis) of the corresponding homotypic responder cell, as determined by 3H-thymidine incorporation. PA-III secretory protein stimulated rat stromal cell proliferation by 1.8-fold. This stimulatory activity of PA-III protein on stromal cell proliferation was partially reduced (approximately 35%) by treatment with nerve growth factor (NGF) antibody, whereas neither acidic fibroblast growth factor (aFGF) antibody nor basic fibroblast growth factor (bFGF) antibody immunoneutralized the stimulatory activity of PA-III cell protein. In the corresponding opposite interaction, rat stromal cell protein modulated PA-III growth in a biphasic manner. At lower concentrations of stromal cell protein (1.25 micrograms/ml) PA-III cell growth was stimulated by 1.6-fold, whereas at higher concentrations of protein (100 micrograms/ml) PA-III cell growth was inhibited to 60%. Treatment of the stromal cell protein (1.25 micrograms/ml and 100 micrograms/ml) with NGF antibody reduced PA-III cell relative growth to approximately 30% and 5%, respectively. bFGF antibody treatment of stromal cell protein at 1.25 micrograms/ml did not influence relative growth, whereas bFGF antibody treatment of 100 micrograms/ml stromal cell protein reduced relative growth by an additional 40%. Treatment of the stromal cell protein (1.25 micrograms/ml and 100 micrograms/ml) with aFGF antibodies reduced relative growth from that observed at these two protein concentrations by approximately 50% in both cases. Human epithelial TSU-pr1 protein stimulated human stromal cell proliferation approximately 1.7-fold. Treatment of TSU-pr1 protein with NGF antibody resulted in stimulation of human stromal cell proliferation (4-fold). In the corresponding opposite interaction, human stromal cell secretory protein stimulated TSU-pr1 epithelial cell proliferation in a dose-dependent manner up to a maximum of 2.6-fold. This stimulation of TSU-pr1 proliferation by stromal cell secretory protein was reduced to 20% of maximal levels by treatment with antibody against NGF, whereas antibodies against bFGF and aFGF did not significantly influence the stimulatory effect of stromal cell secretory protein mediated proliferation of TSU-pr1 cells. These results suggest that prostatic stromal cells and neoplastic epithelial cells secrete several paracrine factors. One of these factors is nerve growth factor-like, and appears to have a major non-neurotrophic influence on the paracrine regulation of prostatic growth.
authors.affiliation: Department of Anatomy and Cell Biology, Georgetown University Medical School, Washington D.C. 20007.
authors.forename: D
authors.initials: D
authors.lastname: Djakiew
authors.forename: B
authors.initials: B
authors.lastname: Pflug
authors.forename: M
authors.initials: M
authors.lastname: Onoda
mesh_terms: D016475:3T3 Cells / Q000166:cytology; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D000818:Animals; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003238:Connective Tissue / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D006133:Growth Substances / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D009928:Organ Specificity; D011467:Prostate / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects
chemical_list: D006133:Growth Substances; D009363:Neoplasm Proteins