Cadherin switching in human prostate cancer progression

The progression of carcinomas is associated with the loss of epithelial mor phology and a concomitant acquisition of a more mesenchymal phenotype, whic h in turn is thought to contribute to the invasive and/or metastatic behavi or of the malignant process. Changes in the expression of cadherins, "cadhe rin switching," plays a critical role during embryogenesis, particularly in morphogenetic processes. Loss of E-cadherin is reported to be associated w ith 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 be en reported in vitro, i.e., 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 mesenc hymal cadherins, in cell lines that lack a functional E-cadherin-catenin ad hesion complex). Here, we report on the immunohistochemical analysis of the expression of N-cadherin and cadherin-ll in human prostate cancer specimen s. N-cadherin was not expressed in normal prostate tissue; however, in pros tatic cancer, N-cadherin was found to be expressed in the poorly differenti ated areas, which showed mainly aberrant or negative E-cadherin staining. C adherin-11 is expressed in the stroma of all prostatic tumors, in the area where stromal and epithelial cells are found. In addition, cadherin-ll is a lso expressed in a dotted pattern or at the membrane of the epithelial cell s of high-grade cancers. In a number of metastatic lesions, N-cadherin and cadherin-ll are expressed homogeneously. These data raise the possibility t hat cadherin switching plays an important role in prostate cancer metastasi s.