Oncotarget

Research Papers:

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

Masakazu Sato, Kei Kawana _, Katsuyuki Adachi, Asaha Fujimoto, Mitsuyo Yoshida, Hiroe Nakamura, Haruka Nishida, Tomoko Inoue, Ayumi Taguchi, Juri Ogishima, Satoko Eguchi, Aki Yamashita, Kensuke Tomio, Osamu Wada-Hiraike, Katsutoshi Oda, Takeshi Nagamatsu, Yutaka Osuga and Tomoyuki Fujii

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Oncotarget. 2017; 8:40935-40945. https://doi.org/10.18632/oncotarget.16783

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Abstract

Masakazu Sato1, Kei Kawana2, Katsuyuki Adachi1, Asaha Fujimoto1, Mitsuyo Yoshida1, Hiroe Nakamura1, Haruka Nishida1, Tomoko Inoue1, Ayumi Taguchi1, Juri Ogishima1, Satoko Eguchi1, Aki Yamashita1, Kensuke Tomio1, Osamu Wada-Hiraike1, Katsutoshi Oda1, Takeshi Nagamatsu1, Yutaka Osuga1 and Tomoyuki Fujii1

1Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

2Department of Obstetrics and Gynecology, School of Medicine, Nihon University, Itabashi-ku, Tokyo, Japan

Correspondence to:

Kei Kawana, email: kkawana-tky@umin.org

Keywords: cancer stem cell (CSC), induced pluripotent stem cell (iPSC), cervical cancer, reserve cell, human leukocyte antigen-G (HLA-G)

Received: June 17, 2016    Accepted: February 27, 2017    Published: April 03, 2017

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.


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