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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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. 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.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.16783</identifier><identifier>PMID: 28402962</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>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</subject><ispartof>Oncotarget, 2017-06, Vol.8 (25), p.40935-40945</ispartof><rights>Copyright: © 2017 Sato et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-5c5e57c3a2a7c4c0d512a61c6f1e4fe7d459cbefd28c824c8ea110b7e93c428f3</citedby><cites>FETCH-LOGICAL-c422t-5c5e57c3a2a7c4c0d512a61c6f1e4fe7d459cbefd28c824c8ea110b7e93c428f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522215/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522215/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28402962$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sato, Masakazu</creatorcontrib><creatorcontrib>Kawana, Kei</creatorcontrib><creatorcontrib>Adachi, Katsuyuki</creatorcontrib><creatorcontrib>Fujimoto, Asaha</creatorcontrib><creatorcontrib>Yoshida, Mitsuyo</creatorcontrib><creatorcontrib>Nakamura, Hiroe</creatorcontrib><creatorcontrib>Nishida, Haruka</creatorcontrib><creatorcontrib>Inoue, Tomoko</creatorcontrib><creatorcontrib>Taguchi, Ayumi</creatorcontrib><creatorcontrib>Ogishima, Juri</creatorcontrib><creatorcontrib>Eguchi, Satoko</creatorcontrib><creatorcontrib>Yamashita, Aki</creatorcontrib><creatorcontrib>Tomio, Kensuke</creatorcontrib><creatorcontrib>Wada-Hiraike, Osamu</creatorcontrib><creatorcontrib>Oda, Katsutoshi</creatorcontrib><creatorcontrib>Nagamatsu, Takeshi</creatorcontrib><creatorcontrib>Osuga, Yutaka</creatorcontrib><creatorcontrib>Fujii, Tomoyuki</creatorcontrib><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</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><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.</description><subject>Cell Differentiation - physiology</subject><subject>Female</subject><subject>Humans</subject><subject>Induced Pluripotent Stem Cells - immunology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Induced Pluripotent Stem Cells - pathology</subject><subject>Neoplastic Stem Cells - immunology</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Regeneration - physiology</subject><subject>Research Paper</subject><subject>Uterine Cervical Neoplasms - immunology</subject><subject>Uterine Cervical Neoplasms - metabolism</subject><subject>Uterine Cervical Neoplasms - pathology</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkdFOHCEUholpU431AXpjuLQXYwcGBsYLE7OpbRMTjbbXhGUOu7QzMAXGxofqOxbd1bXc8Odwzvcf8iP0gdSnRLYN_RS8CVnHFeRT0grZ7KED0rGuopw3b17pfXSU0s-6HM6EpN07tE8lq2nX0gP09xZW4CHq7ILHwWID8d4ZPeAIqUgohWGoBvdroxK2MYx4PY_aY-f72UCPp2GObgoZfMYpw7jtPHE3d4v08QxfYA9_sJ6mGLRZ4xywLaPOr_Bm_wINcedstC96R8I5gs5job9Hb60eEhxt70P04_Lz98XX6ur6y7fFxVVlGKW54oYDF6bRVAvDTN1zQnVLTGsJMAuiZ7wzS7A9lUZSZiRoQuqlgK4pAGmbQ3S-4U7zcoTeFOuoBzVFN-r4oIJ26v8X79ZqFe4V55RSwgvgZAuI4fcMKavRpce_aA9hTopIKRgVou5KK9m0mhhSimBfbEitnpJWu6TVU9Jl5vj1fi8Tz7k2_wCOuazW</recordid><startdate>20170620</startdate><enddate>20170620</enddate><creator>Sato, Masakazu</creator><creator>Kawana, Kei</creator><creator>Adachi, Katsuyuki</creator><creator>Fujimoto, Asaha</creator><creator>Yoshida, Mitsuyo</creator><creator>Nakamura, Hiroe</creator><creator>Nishida, Haruka</creator><creator>Inoue, Tomoko</creator><creator>Taguchi, Ayumi</creator><creator>Ogishima, Juri</creator><creator>Eguchi, Satoko</creator><creator>Yamashita, Aki</creator><creator>Tomio, Kensuke</creator><creator>Wada-Hiraike, Osamu</creator><creator>Oda, Katsutoshi</creator><creator>Nagamatsu, Takeshi</creator><creator>Osuga, Yutaka</creator><creator>Fujii, Tomoyuki</creator><general>Impact Journals LLC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170620</creationdate><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</title><author>Sato, Masakazu ; 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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. 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.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28402962</pmid><doi>10.18632/oncotarget.16783</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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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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