Generation of active TGF-? by prostatic cell cocultures using novel basal and luminal prostatic epithelial cell lines

Abstract

Two prostatic epithelial lines, one of basal origin and one of luminal origin, were established from the dorsolateral prostates of p53 null mice. The cell lines are nontumorigenic when inoculated subcutaneously under the renal capsule or intraprostatically in syngeneic mice. The luminal cell line (PE-L-1) expresses cytokeratins 8 and 18 and the basal cell line (PE-B-1) expresses cytokeratins 5 and 14. The basal cells require serum for growth, whereas the luminal cells grow only in serum-free medium. Both cell lines require the presence of growth factors for optimal growth in culture, with EGF and FGF-2 having the greatest effect on the growth rate. Both lines express androgen receptor (AR) mRNA and protein. Androgen stimulates growth of the basal cell line, indicating that the ARs are functional, whereas growth of the luminal cells is unaffected by androgens. The luminal line is significantly inhibited by exogenous TGF-beta and produces low levels of endogenous TGF-beta. In contrast, the basal cell line produces significant amounts of TGF-beta and its growth is not influenced by this cytokine. Coculture of luminal cells with prostatic smooth muscle cells results in the generation of increased levels of biologically active TGF-beta, indicating a paracrine mechanism of TGF-beta activation that may be involved in the maintenance of normal prostatic function. To our knowledge this is the first report describing both basal and luminal prostatic cell lines from a single inbred animal species and the first indication that prostatic epithelial and stromal cells interact to generate the biologically active form of TGF-beta. These lines will provide an important model for determining basal/luminal interactions in both in vitro and in vivo assays.

Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via β-catenin signaling

“…To quantitatively measure Trop2 localization, a mouse prostate epithelial basal (PEB) cell line (Salm et al 2000) that expresses endogenous Trop2 was used. PEB cells were infected with lentivirus expressing RFP or RFP and Trop2 modified with a C-terminal Myc tag to follow Trop2 ICD.…”

CD73 Expression Is an Independent Prognostic Factor in Prostate Cancer

“…Paradoxically, it also promotes the expression of prometastatic genes and the development of bone metastases (44). TGFb is also important in the normal prostate, where cellular interactions between luminal epithelial cells and stromal cells determine the amount of active TGFb, in order to maintain tissue homeostasis (45). It is our assertion that CD73 expression in normal prostatic epithelium may also be regulated by TGFb.…”

Transforming growth factor ? in the human prostate: Its role in stromal-epithelial interactions in non-cancerous cell culture

“…To the best of our knowledge, this is the ®rst direct demonstration of an increased secretion of TGFb2 by epithelial cells, under the control of a diffusible factor secreted by ®broblasts. In a recent study, the authors demonstrated that co-culture of mice prostate epithelial cell line with smooth muscle cells increases TGFb secretion, but were not able to determine which cell type was the source of this secretion [35]. Other authors have studied the effect of co-culture of prostate epithelial cells and stroma, on epithelial cell growth.…”