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

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 metho...

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Veröffentlicht in:Oncotarget 2017-06, Vol.8 (25), p.40935-40945
Hauptverfasser: Sato, Masakazu, Kawana, Kei, Adachi, Katsuyuki, Fujimoto, Asaha, Yoshida, Mitsuyo, Nakamura, Hiroe, Nishida, Haruka, Inoue, Tomoko, Taguchi, Ayumi, Ogishima, Juri, Eguchi, Satoko, Yamashita, Aki, Tomio, Kensuke, Wada-Hiraike, Osamu, Oda, Katsutoshi, Nagamatsu, Takeshi, Osuga, Yutaka, Fujii, Tomoyuki
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container_end_page 40945
container_issue 25
container_start_page 40935
container_title Oncotarget
container_volume 8
creator Sato, Masakazu
Kawana, Kei
Adachi, Katsuyuki
Fujimoto, Asaha
Yoshida, Mitsuyo
Nakamura, Hiroe
Nishida, Haruka
Inoue, Tomoko
Taguchi, Ayumi
Ogishima, Juri
Eguchi, Satoko
Yamashita, Aki
Tomio, Kensuke
Wada-Hiraike, Osamu
Oda, Katsutoshi
Nagamatsu, Takeshi
Osuga, Yutaka
Fujii, Tomoyuki
description 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.
doi_str_mv 10.18632/oncotarget.16783
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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. 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subjects Cell Differentiation - physiology
Female
Humans
Induced Pluripotent Stem Cells - immunology
Induced Pluripotent Stem Cells - metabolism
Induced Pluripotent Stem Cells - pathology
Neoplastic Stem Cells - immunology
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Regeneration - physiology
Research Paper
Uterine Cervical Neoplasms - immunology
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
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
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