Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer

Tasuku Mariya; Yoshihiko Hirohashi; Toshihiko Torigoe; Yuta Tabuchi; Takuya Asano; Hiroshi Saijo; Takafumi Kuroda; Kazuyo Yasuda; Masahito Mizuuchi; Tsuyoshi Saito; Noriyuki Sato

doi:10.18632/oncotarget.8645

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Research Papers:

Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer

Tasuku Mariya, Yoshihiko Hirohashi _, Toshihiko Torigoe, Yuta Tabuchi, Takuya Asano, Hiroshi Saijo, Takafumi Kuroda, Kazuyo Yasuda, Masahito Mizuuchi, Tsuyoshi Saito and Noriyuki Sato

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Oncotarget. 2016; 7:26806-26822. https://doi.org/10.18632/oncotarget.8645

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Abstract

Tasuku Mariya1,2, Yoshihiko Hirohashi1, Toshihiko Torigoe1, Yuta Tabuchi1,2, Takuya Asano1,2, Hiroshi Saijo1,3, Takafumi Kuroda1,2, Kazuyo Yasuda1, Masahito Mizuuchi1,2, Tsuyoshi Saito2, Noriyuki Sato1

1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan

2Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan

3Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan

Correspondence to:

Yoshihiko Hirohashi, e-mail: [email protected]

Toshihiko Torigoe, e-mail: [email protected]

Keywords: ovarian cancer, cancer stem cell, MMP10, chemoresistance

Received: August 26, 2015 Accepted: March 2, 2016 Published: April 08, 2016

ABSTRACT

Epithelial ovarian cancer (EOC) is one of the most lethal cancers in females. Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) have been reported to be origin of primary and recurrent cancers and to be resistant to several treatments. In this study, we identified matrix metalloproteinase-10 (MMP10) is expressed in CSCs/CICs of EOC. An immunohistochemical study revealed that a high expression level of MMP10 is a marker for poor prognosis and platinum resistance in multivariate analysis. MMP10 gene overexpression experiments and MMP10 gene knockdown experiments using siRNAs revealed that MMP10 has a role in the maintenance of CSCs/CICs in EOC and resistance to platinum reagent. Furthermore, MMP10 activate canonical Wnt signaling by inhibiting noncanonical Wnt signaling ligand Wnt5a. Therefore, MMP10 is a novel marker for CSCs/CICs in EOC and that targeting MMP10 is a novel promising approach for chemotherapy-resistant CSCs/CICs in EOC.

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Research Papers:

Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer

Abstract