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(American Journal of Pathology. 1999;155:1549-1555.)
© 1999 American Society for Investigative Pathology

Regular Articles

Anomalous Cadherin Expression in Osteosarcoma

Possible Relationships to Metastasis and Morphogenesis

Takeshi Kashima^*, Jitsutaro Kawaguchi, Sunao Takeshita, Masahiko Kuroda^*, Masatsugu Takanashi, Hajime Horiuchi^§, Tetsuo Imamura^¶, Yuichi Ishikawa^||, Tsuyoshi Ishida^*, Shigeo Mori^**, Rikuo Machinami^* and Akira Kudo

From the Department of Pathology,^*
Faculty of Medicine, and the Department of Pathology,^**
Institute for Medical Science, University of Tokyo, Tokyo; the Department of Life Science,
Tokyo Institute of Technology, Yokohama; the Department of Laboratory Medicine,
Teikyo University School of Medicine, Tokyo; the Department of Pathology,^§
Toranomon Hospital, Tokyo; the Department of Surgical Pathology,^¶
Teikyo University School of Medicine, Tokyo; and the Department of Pathology,^||
The Cancer Institute, Tokyo, Japan

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 ß-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.

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