Mesothelial cells with mesenchymal features enhance peritoneal dissemination by forming a protumorigenic microenvironment
Malignant ascites accompanied by peritoneal dissemination contain various factors and cell populations as well as cancer cells; however, how the tumor microenvironment is shaped in ascites remains unclear. Single-cell proteomic profiling and a comprehensive proteomic analysis are conducted to compre...
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Published in | Cell reports (Cambridge) Vol. 43; no. 1; p. 113613 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
23.01.2024
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Subjects | |
Online Access | Get full text |
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Summary: | Malignant ascites accompanied by peritoneal dissemination contain various factors and cell populations as well as cancer cells; however, how the tumor microenvironment is shaped in ascites remains unclear. Single-cell proteomic profiling and a comprehensive proteomic analysis are conducted to comprehensively characterize malignant ascites. Here, we find defects in immune effectors along with immunosuppressive cell accumulation in ascites of patients with gastric cancer (GC) and identify five distinct subpopulations of CD45(−)/EpCAM(−) cells. Mesothelial cells with mesenchymal features in CD45(−)/EpCAM(−) cells are the predominant source of chemokines involved in immunosuppressive myeloid cell (IMC) recruitment. Moreover, mesothelial-mesenchymal transition (MMT)-induced mesothelial cells strongly express extracellular matrix (ECM)-related genes, including tenascin-C (TNC), enhancing metastatic colonization. These findings highlight the definite roles of the mesenchymal cell population in the development of a protumorigenic microenvironment to promote peritoneal dissemination.
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•Mesenchymal cells diversity exists in malignant ascites of patients with GC•An immunosuppressive microenvironment is formed in malignant ascites of patients with GC•MMT-induced mesothelial cells produce chemokines involved in IMC recruitment•TNC derived from MMT-induced mesothelial cells enhances metastatic colonization
Yonemura et al. showed that mesothelial cells with mesenchymal features are responsible for the immunosuppressive microenvironment in malignant ascites. MMT-induced mesothelial cells produce chemokines involved in IMC recruitment and enhance attachment to the peritoneum through TNC production as a scaffold for GC cells, leading to enhanced peritoneal dissemination. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2023.113613 |