Cadherins are a family of
calcium-dependent, cell-
cell adhesion molecules that play an important morphoregulatory role in a wide variety of tissues. Alterations in
cadherin function have been implicated in
tumor progression in a number of
adenocarcinomas. Despite the increasing number 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 epithelium. This finding is critical because these cells give rise to the majority of
neoplasms of this organ. Furthermore we demonstrate typical
cadherin features of
cadherin-6, including cytoplasmic binding to alpha- and
beta-catenin. We present data of
cadherin-6 expression in a series of 32 primary
renal cell cancers.
Cadherin-6 expression tended to vary with histology in these samples. Whereas the majority of
renal cell cancers with histology-associated poor prognosis (i.e., high grade clear cell
carcinomas and sarcomatoid renal
tumors) show aberrant expression of
cadherin-6, in
tumors with a favorable prognosis (i.e., low grade clear cell
carcinomas and papillary
cancers), normal
cadherin-6 expression was predominant. Overall, these findings demonstrate specific expression of
cadherin-6 in the proximal renal tubules in normal human kidney and suggest that alterations of
cadherin-6 expression are associated with progression of
renal cell carcinoma.