PMID- 38232734
OWN - NLM
STAT- MEDLINE
DCOM- 20240126
LR  - 20240212
IS  - 2211-1247 (Electronic)
VI  - 43
IP  - 1
DP  - 2024 Jan 23
TI  - Mesothelial cells with mesenchymal features enhance peritoneal dissemination by 
      forming a protumorigenic microenvironment.
PG  - 113613
LID - S2211-1247(23)01625-X [pii]
LID - 10.1016/j.celrep.2023.113613 [doi]
AB  - 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.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Yonemura, Atsuko
AU  - Yonemura A
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan; Division of Carcinogenesis, The Cancer Institute, 
      Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
FAU - Semba, Takashi
AU  - Semba T
AD  - Gastrointestinal Cancer Biology, International Research Center of Medical 
      Sciences (IRCMS), Kumamoto University, Kumamoto 860-0811, Japan; Division of 
      Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, 
      Tokyo 135-8550, Japan.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan; Division of Carcinogenesis, The Cancer Institute, 
      Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
FAU - Fan, Yibo
AU  - Fan Y
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Yasuda-Yoshihara, Noriko
AU  - Yasuda-Yoshihara N
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan.
FAU - Wang, Huaitao
AU  - Wang H
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan; Division of Carcinogenesis, The Cancer Institute, 
      Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
FAU - Uchihara, Tomoyuki
AU  - Uchihara T
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan.
FAU - Yasuda, Tadahito
AU  - Yasuda T
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan.
FAU - Nishimura, Akiho
AU  - Nishimura A
AD  - Gastrointestinal Cancer Biology, International Research Center of Medical 
      Sciences (IRCMS), Kumamoto University, Kumamoto 860-0811, Japan; Division of 
      Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, 
      Tokyo 135-8550, Japan.
FAU - Fu, Lingfeng
AU  - Fu L
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan; Division of Carcinogenesis, The Cancer Institute, 
      Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
FAU - Hu, Xichen
AU  - Hu X
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan; Division of Carcinogenesis, The Cancer Institute, 
      Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
FAU - Wei, Feng
AU  - Wei F
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan.
FAU - Kitamura, Fumimasa
AU  - Kitamura F
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan.
FAU - Akiyama, Takahiko
AU  - Akiyama T
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan.
FAU - Yamashita, Kohei
AU  - Yamashita K
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan.
FAU - Eto, Kojiro
AU  - Eto K
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan.
FAU - Iwagami, Shiro
AU  - Iwagami S
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan.
FAU - Iwatsuki, Masaaki
AU  - Iwatsuki M
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan.
FAU - Miyamoto, Yuji
AU  - Miyamoto Y
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan.
FAU - Matsusaki, Keisuke
AU  - Matsusaki K
AD  - Ascites Treatment Center, Kanamecho Hospital, Tokyo 171-0043, Japan.
FAU - Yamasaki, Juntaro
AU  - Yamasaki J
AD  - Division of Gene Regulation, Institute for Advanced Medical Research, School of 
      Medicine, Keio University, Tokyo 160-8582, Japan; Division of Gene Regulation, 
      Cancer Center, Fujita Health University, Toyoake 470-1192, Japan.
FAU - Nagano, Osamu
AU  - Nagano O
AD  - Division of Gene Regulation, Institute for Advanced Medical Research, School of 
      Medicine, Keio University, Tokyo 160-8582, Japan; Division of Gene Regulation, 
      Cancer Center, Fujita Health University, Toyoake 470-1192, Japan.
FAU - Saya, Hideyuki
AU  - Saya H
AD  - Division of Gene Regulation, Institute for Advanced Medical Research, School of 
      Medicine, Keio University, Tokyo 160-8582, Japan; Division of Gene Regulation, 
      Cancer Center, Fujita Health University, Toyoake 470-1192, Japan.
FAU - Song, Shumei
AU  - Song S
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX 77030, USA.
FAU - Tan, Patrick
AU  - Tan P
AD  - Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 
      169857, Singapore.
FAU - Baba, Hideo
AU  - Baba H
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Center for Metabolic Regulation of 
      Healthy Aging, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, 
      Japan.
FAU - Ajani, Jaffer A
AU  - Ajani JA
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD 
      Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: 
      jajani@mdanderson.org.
FAU - Ishimoto, Takatsugu
AU  - Ishimoto T
AD  - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, 
      Kumamoto University, Kumamoto 860-8556, Japan; Gastrointestinal Cancer Biology, 
      International Research Center of Medical Sciences (IRCMS), Kumamoto University, 
      Kumamoto 860-0811, Japan; Division of Carcinogenesis, The Cancer Institute, 
      Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan. Electronic 
      address: takatsugu.ishimoto@jfcr.or.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240116
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Epithelial Cell Adhesion Molecule)
SB  - IM
MH  - Humans
MH  - *Ascites/pathology
MH  - Epithelial Cell Adhesion Molecule
MH  - Proteomics
MH  - Peritoneum/pathology
MH  - *Peritoneal Neoplasms/pathology
MH  - Cell Line, Tumor
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - CP: Cancer
OT  - IMCs
OT  - MDSCs
OT  - ascites
OT  - extracellular matrix
OT  - gastric cancer
OT  - mass cytometry
OT  - mesenchymal cells
OT  - mesothelial cells
OT  - peritoneal dissemination
OT  - tenascin-C
OT  - tumor microenvironment
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2024/01/18 00:42
MHDA- 2024/01/26 06:43
CRDT- 2024/01/17 18:42
PHST- 2023/02/03 00:00 [received]
PHST- 2023/09/13 00:00 [revised]
PHST- 2023/12/07 00:00 [accepted]
PHST- 2024/01/26 06:43 [medline]
PHST- 2024/01/18 00:42 [pubmed]
PHST- 2024/01/17 18:42 [entrez]
AID - S2211-1247(23)01625-X [pii]
AID - 10.1016/j.celrep.2023.113613 [doi]
PST - ppublish
SO  - Cell Rep. 2024 Jan 23;43(1):113613. doi: 10.1016/j.celrep.2023.113613. Epub 2024 
      Jan 16.