Mesothelin promotes the migration of endometrioid carcinoma and is associated with the MELF pattern

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2024-08-24 DOI:10.1016/j.prp.2024.155562

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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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间皮素促进子宫内膜样癌的迁移，并与 MELF 模式有关。

间皮素（MSLN）在正常组织的间皮细胞中表达，但在各种恶性肿瘤中过度表达。在这项研究中，我们利用激光显微切割和 RNA 测序技术，寻找在具有 MELF（微囊状、拉长和破碎）模式的子宫内膜样癌（EC）病例中表达较多的基因，结果发现 MSLN 在具有 MELF 模式的病例中主要表达。通过建立MSLN基因敲除和敲除的EC细胞系，分析了MSLN在EC中的作用。MSLN促进了迁移和上皮-间质转化（EMT）。此外，我们还发现粘连蛋白-6（CDH6）的表达受 MSLN 调节。众所周知，MSLN能与癌症抗原125（CA125）结合，而我们发现CA125能通过MSLN调控CDH6的表达。免疫组化研究表明，MELF模式的癌细胞中MSLN、CA125和CDH6的表达水平显著升高。CA125 的表达不仅在免疫组化染色强度上与 MSLN 相似，而且在血中 CA125 的水平上也与 MSLN 相似。我们的研究结果表明，MSLN通过上游的CA125和下游的CDH6促进了EC细胞的迁移和EMT。因此，MSLN有可能成为具有MELF模式的EC的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.

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