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Integrin α5 mediates cancer cell-fibroblast adhesion and peritoneal dissemination of diffuse-type gastric carcinoma.
Miyamoto, Shingo; Nagano, Yoshiko; Miyazaki, Makoto; Nagamura, Yuko; Sasaki, Kazuki; Kawamura, Takeshi; Yanagihara, Kazuyoshi; Imai, Toshio; Ohki, Rieko; Yashiro, Masakazu; Tanaka, Masato; Sakai, Ryuichi; Yamaguchi, Hideki.
Affiliation
  • Miyamoto S; Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Tokyo, Japan.
  • Nagano Y; Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Tokyo, Japan.
  • Miyazaki M; Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Tokyo, Japan.
  • Nagamura Y; Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Tokyo, Japan.
  • Sasaki K; Department of Peptidomics, Sasaki Institute, Sasaki Foundation, Tokyo, Japan.
  • Kawamura T; Proteomics Laboratory, Isotope Science Center, The University of Tokyo, Tokyo, Japan.
  • Yanagihara K; Division of Biomarker Discovery, Exploratory Oncology & Clinical Trial Center, National Cancer Center, Chiba, Japan.
  • Imai T; Department of Animal Experimentation, National Cancer Center Research Institute, Tokyo, Japan.
  • Ohki R; Laboratory of Fundamental Oncology, National Cancer Center Research Institute, Tokyo, Japan.
  • Yashiro M; Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
  • Tanaka M; Laboratory of Immune Regulation, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
  • Sakai R; Department of Biochemistry, Kitasato University School of Medicine, Kanagawa, Japan.
  • Yamaguchi H; Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Tokyo, Japan. Electronic address: h-yamaguchi@po.kyoundo.jp.
Cancer Lett ; 526: 335-345, 2022 02 01.
Article in En | MEDLINE | ID: mdl-34775002
Diffuse-type gastric carcinoma (DGC) has a poor prognosis due to its rapid diffusive infiltration and frequent peritoneal dissemination. DGC is associated with massive fibrosis caused by aberrant proliferation of cancer-associated fibroblasts (CAFs). Previously, we reported that direct heterocellular interaction between cancer cells and CAFs is important for the peritoneal dissemination of DGC. In this study, we aimed to identify and target the molecules that mediate such heterocellular interactions. Monoclonal antibodies (mAbs) against intact DGC cells were generated and subjected to high-throughput screening to obtain several mAbs that inhibit the adhesion of DGC cells to CAFs. Immunoprecipitation and mass spectrometry revealed that all mAbs recognized integrin α5 complexed with integrin ß1. Blocking integrin α5 in DGC cells or fibronectin, a ligand of integrin α5ß1, deposited on CAFs abrogated the heterocellular interaction. Administration of mAbs or knockout of integrin α5 in DGC cells suppressed their invasion led by CAFs in vitro and peritoneal dissemination in a mouse xenograft model. Altogether, these findings demonstrate that integrin α5 mediates the heterotypic cancer cell-fibroblast interaction during peritoneal dissemination of DGC and may thus be a therapeutic target.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stomach Neoplasms / Integrin alpha5 / Fibroblasts Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Cancer Lett Year: 2022 Document type: Article Affiliation country: Japan Country of publication: Ireland

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stomach Neoplasms / Integrin alpha5 / Fibroblasts Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Journal: Cancer Lett Year: 2022 Document type: Article Affiliation country: Japan Country of publication: Ireland