ID | 66910 |
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Hassan, Ghmkin
Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
Afify, Said M.
Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
Zahra, Maram H.
Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
Nawara, Hend M.
Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
Kumon, Kazuki
Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
Salomon, David S.
Center for Cancer Research, National Cancer Institute
Seno, Akimasa
Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
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Seno, Masaharu
Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
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Abstract | Induced pluripotent stem cells (iPSCs) are useful tools for modeling diseases and developing personalized medicine. We have been developing cancer stem cells (CSCs) from iPSCs with conditioned medium (CM) of cancer-derived cells as the mimicry of the microenvironment of tumor initiation. However, the conversion of human iPSCs has not always been efficient with only CM. In this study, human iPSCs reprogrammed from monocytes of healthy volunteers were cultured in a media containing 50% of the CM from human pancreatic cancer derived BxPC3 cells supplemented with a MEK inhibitor (AZD6244) and a GSK-3α/β inhibitor (CHIR99021). The survived cells were assessed for the characteristics of CSCs in vitro and in vivo. As a result, they exhibited CSC phenotypes of self-renewal, differentiation, and malignant tumorigenicity. Primary culture of the malignant tumors of the converted cells exhibited the elevated expression of CSC related genes CD44, CD24 and EPCAM maintaining the expression of stemness genes. In conclusion, the inhibition of GSK-3α/β and MEK and the microenvironment of tumor initiation mimicked by the CM can convert human normal stem cells into CSCs. This study could provide insights into establishing potentially novel personalized cancer models which could help investigate the tumor initiation and screening of personalized therapies on CSCs.
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Keywords | Cancer stem cells
Human iPSCs
Signal pathway inhibitors
Tumor initiation
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Note | The version of record of this article, first published in Cytotechnology, is available online at Publisher’s website: http://dx.doi.org/10.1007/s10616-023-00575-1
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Published Date | 2023-04-01
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Publication Title |
Cytotechnology
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Volume | volume75
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Issue | issue3
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Publisher | Springer Science and Business Media LLC
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Start Page | 243
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End Page | 253
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ISSN | 0920-9069
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NCID | AA10678299
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © The Author(s) 2023
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.1007/s10616-023-00575-1
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License | http://creativecommons.org/licenses/by/4.0/
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Citation | Hassan, G., Afify, S.M., Zahra, M.H. et al. GSK-3α/β and MEK inhibitors assist the microenvironment of tumor initiation. Cytotechnology 75, 243–253 (2023). https://doi.org/10.1007/s10616-023-00575-1
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Funder Name |
Okayama University
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