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 intact form has a typical
cadherin structure, whereas the variant form, generated by alternative splicing, encodes a cytoplasmic domain that is completely different from that of the intact form and lacks a homophilic cell-cell adhesion ability. At the
protein level, the secreted form generated from the intact
cadherin-11 is present. We examined the expression of the intact and the variant forms of
cadherin-11 in 23 primary and metastatic
osteosarcomas from 22 patients by
reverse transcriptase-polymerase chain reaction (RT-PCR) analyses, revealing that all 23
tumors in the patients expressed the variant form and three of them expressed it prominently. On the other hand, Western blot analyses of six
tumors showed that the secreted form was strongly expressed, and furthermore, expression of
N-cadherin was extremely low. Overexpression of the intact
cadherin-11 cDNA in
osteosarcoma cell lines demonstrated that the secreted form is derived from the intact form of
cadherin-11 in
osteosarcoma. Immunohistochemically,
cadherin-11,
N-cadherin, and
beta-catenin were expressed at the cell surface of fetal osteoblasts, whereas in
osteosarcoma cells, they were expressed only focally or weakly in the cytoplasm. Considering the function of
cadherin in
carcinomas, it is suggested that the anomalous expression of human
cadherin-11 in
osteosarcoma and the reduced expression of
N-cadherin play a role in
metastasis and the irregular morphology in the highly
malignant mesenchymal tumor.