title: Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): A new approach to finding targets for cervical cancer stem cell treatment.
abstract: Cervical reserve cells are epithelial progenitor cells that are pathologically evident as the origin of cervical cancer. Thus, investigating the characteristics of cervical reserve cells could yield insight into the features of cervical cancer stem cells (CSCs). In this study, we established a method for the regeneration of cervical reserve cell-like properties from human induced pluripotent stem cells (iPSCs) and named these cells induced reserve cell-like cells (iRCs). Approximately 70% of iRCs were positive for the reserve cell markers p63, CK5 and CK8. iRCs also expressed the SC junction markers CK7, AGR2, CD63, MMP7 and GDA. While iRCs expressed neither ERα nor ERβ, they expressed CA125. These data indicated that iRCs possessed characteristics of cervical epithelial progenitor cells. iRCs secreted higher levels of several inflammatory cytokines such as macrophage migration inhibitory factor (MIF), soluble intercellular adhesion molecule 1 (sICAM-1) and C-X-C motif ligand 10 (CXCL-10) compared with normal cervical epithelial cells. iRCs also expressed human leukocyte antigen-G (HLA-G), which is an important cell-surface antigen for immune tolerance and carcinogenesis. Together with the fact that cervical CSCs can originate from reserve cells, our data suggested that iRCs were potent immune modulators that might favor cervical cancer cell survival. In conclusion, by generating reserve cell-like properties from iPSCs, we provide a new approach that may yield new insight into cervical cancer stem cells and help find new oncogenic targets.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Nihon University, Itabashi-ku, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Asaha
authors.initials: A
authors.lastname: Fujimoto
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Nishida
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Juri
authors.initials: J
authors.lastname: Ogishima
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Eguchi
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Tomio
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Wada-Hiraike
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagamatsu
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012038:Regeneration / Q000502:physiology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
keywords: cancer stem cell (CSC); cervical cancer; human leukocyte antigen-G (HLA-G); induced pluripotent stem cell (iPSC); reserve cell