CADHERIN-6, A CELL-ADHESION MOLECULE SPECIFICALLY EXPRESSED IN THE PROXIMAL RENAL TUBULE AND RENAL-CELL CARCINOMA

Cadherins are a family of calcium-dependent, cell-cell adhesion molecu les that play an important morphoregulatory role in a wide variety of tissues. Alterations in cadherin function have been implicated in tumo r progression in a number of adenocarcinomas. Despite the increasing n umber of new cadherins identified, little is known about cadherins in normal renal tissue and renal carcinomas. A novel cadherin transcript, cadherin-6, was recently described to be present in renal cancer cell lines and fetal kidney, but no data on protein expression nor tissue localization has been reported. In this study, we demonstrate that the expression of cadherin-6 is restricted to the proximal tubule epithel ium. This finding is critical because these cells give rise to the maj ority of neoplasms of this organ. Furthermore we demonstrate typical c adherin features of cadherin-6, including cytoplasmic binding to alpha - and beta-catenin. We present data of cadherin-6 expression in a seri es of 32 primary renal cell cancers. Cadherin-6 expression tended to v ary with histology in these samples. Whereas the majority of renal cel l cancers with histology-associated poor prognosis (i.e., high grade c lear cell carcinomas and sarcomatoid renal tumors) show aberrant expre ssion of cadherin-6, in tumors with a favorable prognosis (i.e., low g rade clear cell carcinomas and papillary cancers), normal cadherin-6 e xpression was predominant. Overall, these findings demonstrate specifi c expression of cadherin-6 in the proximal renal tubules in normal hum an kidney and suggest that alterations of cadherin-6 expression are as sociated with progression of renal cell carcinoma.