N-cadherin expression in human prostate carcinoma cell lines - An epithelial-mesenchymal transformation mediating adhesion with stromal cells

In human prostate adenocarcinoma, an association between loss of E-cadherin , increased Gleason score, and extracapsular dissemination has been observe d. Further characterization of the E-cadherin/catenin phenotype of human pr ostate carcinoma cell lines showed loss of E-cadherin and expression of N-c adherin in poorly differentiated prostate carcinoma cell lines (PC-3N deriv ed from PC-3, PC-3, and JCA1). We showed that N-cadherin is concentrated at sites of cell-cell contact in PC-3N cellular extensions. N-cadherin was al so expressed in prostate stromal fibroblasts both in vitro and in prostate tissue. Go-cultures of prostate stromal fibroblasts and PC-3N cells showed the immunolocalization of N-cadherin in intercellular contacts. In addition , the isoform expression of the cadherin binding protein p120(ctn) differed in relation to the expression of E- versus N-cadherin by the prostate carc inoma cell lines. The p100 isoform was more highly expressed in E-cadherin- positive carcinoma cell lines, whereas p120 was predominantly expressed onl y in N-cadherin-positive prostate carcinoma cell lines and prostate stromal fibroblasts, The N-cadherin-positive carcinoma cell line, PC-3N, displayed aggressive invasion into the surface of the diaphragm muscle after intrape ritoneal injection of SCID mice. The gain of N-cadherin and loss of E-cadhe rin by invasive prostate carcinoma cell Lines suggests a progression from a n epithelial to a mesenchymal phenotype, which may allow for their interact ion with surrounding stromal fibroblasts and facilitate metastasis.