Tissue factor pathway inhibitor-2 inhibits integrin β1 activation and focal adhesion formation and suppresses peritoneal ovarian cancer dissemination in mice.

Autor: Ota Y; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan; Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa Ward, Yokohama, Kanagawa, 236-0004, Japan; Cancer Biology Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan., Uomoto M; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan; Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa Ward, Yokohama, Kanagawa, 236-0004, Japan., Koizume S; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan., Sato S; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan., Hoshino D; Cancer Biology Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan., Yoshihara M; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan., Nakamura Y; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan., Tadokoro H; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan., Myoba S; Bioscience Division, Research and Development Department, Tosoh Corporation, 2743-1, Hayakawa, Ayase, Kanagawa, 252-1123, Japan., Ohtake N; Bioscience Division, Research and Development Department, Tosoh Corporation, 2743-1, Hayakawa, Ayase, Kanagawa, 252-1123, Japan., Miyagi E; Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa Ward, Yokohama, Kanagawa, 236-0004, Japan., Miyagi Y; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa, 241-8515, Japan. Electronic address: miyagi.0e82r@kanagawa-pho.jp.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 03; Vol. 736, pp. 150890. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1016/j.bbrc.2024.150890
Abstrakt: Tissue factor pathway inhibitor-2 (TFPI2) is a Kunitz-type serine protease inhibitor and an ovarian clear cell carcinoma (CCC) biomarker. TFPI2 is expressed in several cancers and exerts tumor-suppressive effects; however, the role of TFPI2 in the CCC cell phenotype remains unclear. Therefore, in this study, we investigated the function of TFPI2 by establishing a gene knockout (KO) in ES-2 CCC cells and observed the change in phenotypes in vitro and in vivo. TFPI2 KO inhibited ES-2 cell proliferation, increased extracellular matrix protein adhesion, enhanced focal adhesion formation and activated integrin β1 cell surface clustering in vitro, and markedly increased ES-2 tumor growth and dissemination in the peritoneal cavity of a mouse xenograft model. These findings suggest a novel function of TFPI2 expression in suppressing the formation of focal adhesions in CCC cells, potentially by activating integrin β1. This function plays a role in the peritoneal growth characteristics of CCC cells.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yohei Miyagi reports financial support was provided by Tosoh Corporation. Shohei Myoba reports a relationship with Tosoh Corporation that includes: employment. Norihisa Ohtake reports a relationship with Tosoh Corporation that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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