Anomalous cadherin expression in osteosarcoma - Possible relationships to metastasis and morphogenesis

Two isoforms Of the human cadherin-11/OB-cadherin gene, the intact and the variant forms, had been isolated from an osteosarcoma cDNA library. The int act form has a typical cadherin structure, whereas the variant form, genera ted by alternative splicing, encodes a cytoplasmic domain that is completel y different from that of the intact form and lacks a homophilic cell-cell a dhesion ability. At the protein level, the secreted form generated from the intact cadherin-11 is present. We examined the expression of the intact an d the variant forms of cadherin-11 in 23 primary and metastatic osteosarcom as from 22 patients by reverse transcriptase-polymerase chain reaction (RT- PCR) analyses, revealing that all 23 tumors in the patients expressed the v ariant form and three of them expressed it prominently. On the other hand, Western blot analyses of six tumors showed that the secreted form was stron gly expressed, and furthermore, expression of N-cadherin was extremely low. Overexpression of the intact cadherin-11 cDNA in osteosarcoma cell lines d emonstrated that the secreted form is derived from the intact form of cadhe rin-11 in osteosarcoma. Immunohistochemically, cadherin-11, N-cadherin, and beta-catenin were expressed at the cell surface of fetal osteoblasts, wher eas in osteosarcoma cells, they were expressed only focally or weakly in th e cytoplasm. Considering the function of cadherin in carcinomas, it is sugg ested that the anomalous expression of human cadherin-11 in osteosarcoma an d the reduced expression of N-cadherin play a role in metastasis and the ir regular morphology in the highly malignant mesenchymal tumor.