title: 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: 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.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Mariya
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tabuchi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saijo
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kuroda
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Mizuuchi
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D000077216:Carcinoma, Ovarian Epithelial; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016016:Proportional Hazards Models; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10
keywords: MMP10; cancer stem cell; chemoresistance; ovarian cancer