Frequent mesothelial-to-mesenchymal transition in colorectal cancer contributes to an immunosuppressive microenvironment.

IF 3.4 3区 医学 Q1 PATHOLOGY
Shiori Watabe, Yoshinao Kikuchi, Daisuke Komura, Masato Watanabe, Masahiro Kato, Hiroshi Uozaki
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引用次数: 0

Abstract

The mesothelial-to-mesenchymal transition (MMT) is the process by which mesothelial cells transform into fibroblast-like cells and migrate into the stroma. Recently, antigen-presenting cancer associated fibroblasts (apCAFs) have been shown to originate from mesothelial cells undergoing MMT and establish an immunosuppressive microenvironment by inducing regulatory T cells (Tregs). It remains unclear whether MMT occurs universally across various cancer types during peritoneal dissemination as a physiological reaction or if its occurrence depends on the organ of origin and tumor characteristics. This study investigated MMT induction and its significance in primary and peritoneal disseminated lesions of colorectal adenocarcinoma (CRAC) and gastric adenocarcinoma (GAC). Analysis of publicly available single-cell RNA sequence data confirmed the presence of MMT-induced cells in both cancer types. Histopathologically, immunohistochemical studies revealed MMT induction in 75.3% of CRAC and 31.0% of GAC primary lesions, and in 67.6% of CRAC and 20.5% of GAC disseminated lesions. MMT induction was more frequent in CRAC than in GAC, even at the same sites of dissemination. In CRAC, MMT was more frequently observed in tubular than in non-tubular adenocarcinoma. Furthermore, the number of apCAFs and Tregs increased with the degree of MMT induction in disseminated CRAC lesions, showing a positive correlation between their numbers. This study demonstrates that MMT is not merely a physiological reaction to cancer invasion, but is induced by cancer, with its extent varying by different cancer types. The induction of the MMT in disseminated CRAC lesions may play a significant role in establishing an immunosuppressive microenvironment.

结直肠癌中频繁的间皮向间质转化有助于免疫抑制微环境。
间充质转化(MMT)是指间皮细胞向成纤维细胞样细胞转化并向间质迁移的过程。最近,抗原呈递癌相关成纤维细胞(apCAFs)已被证明起源于接受MMT的间皮细胞,并通过诱导调节性T细胞(Tregs)建立免疫抑制微环境。目前尚不清楚MMT是作为一种生理反应在腹膜传播过程中普遍发生在各种癌症类型中,还是取决于起源器官和肿瘤特征。本研究探讨MMT在结肠腺癌(CRAC)和胃腺癌(GAC)原发性和腹膜弥散性病变中的诱导作用及其意义。对公开获得的单细胞RNA序列数据的分析证实了mmt诱导细胞在两种癌症类型中的存在。组织病理学上,免疫组化研究显示,MMT诱导了75.3%的CRAC和31.0%的GAC原发病变,67.6%的CRAC和20.5%的GAC弥散性病变。即使在相同的传播部位,CRAC的MMT诱导也比GAC更频繁。在CRAC中,MMT在管状腺癌中比在非管状腺癌中更常见。此外,在弥散性CRAC病变中,apCAFs和Tregs的数量随着MMT诱导程度的增加而增加,两者之间呈正相关关系。本研究表明,MMT不仅仅是一种针对癌症侵袭的生理反应,而且是由癌症诱导的,其程度因癌症类型的不同而不同。在弥散性CRAC病变中诱导MMT可能在建立免疫抑制微环境中起重要作用。
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
Virchows Archiv
Virchows Archiv 医学-病理学
CiteScore
7.40
自引率
2.90%
发文量
204
审稿时长
4-8 weeks
期刊介绍: Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.
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