Cadherin switching in human prostate cancer progression

Abstract

The progression of carcinomas is associated with the loss of epithelial morphology and a concomitant acquisition of a more mesenchymal phenotype, which in turn is thought to contribute to the invasive and/or metastatic behavior of the malignant process. Changes in the expression of cadherins, "cadherin switching," plays a critical role during embryogenesis, particularly in morphogenetic processes. Loss of E-cadherin is reported to be associated with a poor prognosis; however, thus far, evidence (R. Umbas, et al., Cancer Res. 54: 3929-3933, 1994) for up-regulation of other cadherins has only been reported in vitro, ie., we have found evidence (M. J. G. Bussemakers et al., Int. J. Cancer, 85: 446-450, 2000) for cadherin switching in prostate cancer cell lines (up-regulation of N-cadherin and cadherin-11, two mesenchymal cadherins, in cell lines that lack a functional E-cadherin-catenin adhesion complex). Here, we report on the immunohistochemical analysis of the expression of N-cadherin and cadherin-11 in human prostate cancer specimens. N-cadherin was not expressed in normal prostate tissue; however, in prostatic cancer, N-cadherin was found to be expressed in the poorly differentiated areas, which showed mainly aberrant or negative E-cadherin staining. Cadherin-11 is expressed in the stroma of all prostatic tumors, in the area where stromal and epithelial cells are found. In addition, cadherin-11 is also expressed in a dotted pattern or at the membrane of the epithelial cells of high-grade cancers. In a number of metastatic lesions, N-cadherin and cadherin-11 are expressed homogeneously. These data raise the possibility that cadherin switching plays an important role in prostate cancer metastasis.