Significance and function of cadherin-11 in breast cancer

The cadherins are a family of cell adhesion molecules that have been investigated extensively with regard to their putative roles in cancer progression. One cadherin in particular, cadherin-11, is expressed in aggressive epithelial cancers, including signet ring cell carcinoma, despite its normal expression only in mesenchymal tissue. In addition, aberrant expression of cadherin-11 was found in the most invasive breast cancer cell lines. Little is known about the function of cadherin-11, however. It is a Type II cadherin, exhibiting relative homology to well known cadherins such as E- and N-cadherin. Cad-11 is unique, however, in that its expression is accompanied by the expression of a splice variant, termed cadherin-11 variant. The variant form of cad-11 possesses an extracellular domain and a partial transmembrane identical to cadherin-11 intact, but at the point of splicing a frameshift confers a unique cytoplasmic domain. The expression pattern seen in aggressive carcinomas and breast cancer cell lines suggest that expression of cadherin-11-intact and/or variant could be causal or correlative in the acquisition of an invasive phenotype. In order to test this hypothesis, we produced several antibodies specifically recognizing cadherin-11. In addition, we investigated the expression of cadherin-11 intact in breast carcinoma samples. Finally, we studied the effects of exogenous cadherin-11 expression in two well-differentiated breast cancer cell lines, SKBR3 and MCF7. We found that cadhern-11 is expressed in all stages of breast carcinoma, but may exhibit an increased incidence in bone metastases. In addition, exogenous expression of cadherin-11 intact and variant induced increased invasive activity in both cell lines, suggesting that cadherin-11 may indeed be causal in the acquisition of an invasive phenotype in breast cancer.