Abstract
Mesothelin (MSLN) is expressed in the mesothelium in normal tissues but is overexpressed in various malignant tumors. In this study, we searched for genes that were more frequently expressed in cases of endometrioid carcinoma (EC) with the MELF (microcystic, elongated, and fragmented) pattern using laser microdissection and RNA sequencing, and found that MSLN was predominantly expressed in cases with the MELF pattern. The role of MSLN in EC was analyzed by generating MSLN-knockout and -knockdown EC cell lines. MSLN promoted migration and epithelial–mesenchymal transition (EMT). Moreover, we found that cadherin-6 (CDH6) expression was regulated by MSLN. MSLN is known to bind to cancer antigen 125 (CA125), and we found that CA125 can regulate CDH6 expression via MSLN. Immunohistochemical investigations showed that MSLN, CA125, and CDH6 expression levels were considerably elevated in EC with the MELF pattern. The expression of CA125 was similar to that of MSLN not only in terms of immunohistochemical staining intensity but also the blood level of CA125. Our results showed that MSLN contributes to the migration and EMT of EC cells through upstream CA125 and downstream CDH6. Therefore, MSLN has potential as a therapeutic target for EC with the MELF pattern.
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