Mesothelial cells with mesenchymal features enhance peritoneal dissemination by forming a protumorigenic microenvironment

被引：15

作者：

Yonemura, Atsuko ^{[1
,2
,3
]}

Semba, Takashi ^{[2
,3
]}

Zhang, Jun ^{[1
,3
]}

Fan, Yibo ^{[4
]}

Yasuda-Yoshihara, Noriko ^{[1
,2
]}

Wang, Huaitao ^{[1
,2
,3
]}

Uchihara, Tomoyuki ^{[1
,2
]}

Yasuda, Tadahito ^{[1
,2
]}

Nishimura, Akiho ^{[2
,3
]}

Fu, Lingfeng ^{[2
,3
]}

Hu, Xichen ^{[3
]}

Wei, Feng ^{[1
,2
]}

Kitamura, Fumimasa ^{[1
,2
]}

Akiyama, Takahiko ^{[1
,2
]}

Yamashita, Kohei ^{[1
]}

Eto, Kojiro ^{[1
]}

Iwagami, Shiro ^{[1
]}

Iwatsuki, Masaaki ^{[1
]}

Miyamoto, Yuji ^{[1
]}

Matsusaki, Keisuke ^{[5
]}

Yamasaki, Juntaro ^{[6
,7
]}

Nagano, Osamu ^{[6
,7
]}

Saya, Hideyuki ^{[6
,7
]}

Song, Shumei ^{[4
]}

Tan, Patrick ^{[8
]}

Baba, Hideo ^{[1
,9
]}

Ajani, Jaffer A. ^{[4
]}

Ishimoto, Takatsugu ^{[1
,2
,3
]}

机构：

[1] Kumamoto Univ, Grad Sch Med Sci, Dept Gastroenterol Surg, Kumamoto 8608556, Japan

[2] Kumamoto Univ, Int Res Ctr Med Sci IRCMS, Gastrointestinal Canc Biol, Kumamoto 8600811, Japan

[3] Japanese Fdn Canc Res, Canc Inst, Div Carcinogenesis, Tokyo 1358550, Japan

[4] Univ Texas MD Anderson Canc Ctr Houston, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA

[5] Kanamecho Hosp, Ascites Treatment Ctr, Tokyo 1710043, Japan

[6] Keio Univ, Inst Adv Med Res, Div Gene Regulat, Sch Med, Tokyo 1608582, Japan

[7] Fujita Hlth Univ, Canc Ctr, Div Gene Regulat, Toyoake 4701192, Japan

[8] Duke NUS Med Sch, Program Canc & Stem Cell Biol, Singapore 169857, Singapore

[9] Kumamoto Univ, Fac Life Sci, Ctr Metab Regulat Hlth Aging, Kumamoto 8608556, Japan

来源：

CELL REPORTS | 2024年 / 43卷 / 01期

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

TENASCIN-C; METASTASIS; TRANSITION; EXPRESSION;

D O I：

10.1016/j.celrep.2023.113613

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. Singlecell 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.

引用

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