ID | 63156 |
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Hassan, Ghmkin
Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
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Ohara, Toshiaki
Department of Pathology and Experimental Medicine, Medical School, Okayama University
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Afify, Said M.
Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
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Kumon, Kazuki
Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Zahra, Maram H.
Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Fu, Xiaoying
Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Al Kadi, Mohamad
Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University
Seno, Akimasa
Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
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Salomon, David S.
Mouse genetics program, Center for Cancer Research, National Cancer Institute
Seno, Masaharu
Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
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Abstract | Background
Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. Here, we demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo. Methods Three different pancreatic cancer line cells, BxPC3, PANC1, and PK8 cells were mixed with miPSCs and subcutaneously injected into immunodeficient mice. Tumors were evaluated by histological analysis and cells derived from iPSCs were isolated and selected from tumors. The isolated cells were characterized for cancer stem cell characters in vitro and in vivo as well as their responses to anticancer drugs. The impact of co-injection of iPSCs with cancer cells on transcriptome and signaling pathways of iPSCs was investigated. Results The injection of miPSCs mixed with human pancreatic cancer cells into immunodeficient mice maintained the stemness of miPSCs and changed their phenotype. The miPSCs acquired CSC characteristics of tumorigenicity and self-renewal. The drug responses and the metastatic ability of CSCs converted from miPSCs varied depending on the microenvironment of cancer cells. Interestingly, transcriptome profiles of these cells indicated that the pathways related with aggressiveness and energy production were upregulated from the levels of miPSCs. Conclusions Our result suggests that cancer-inducing microenvironment in vivo could rewire the cell signaling and metabolic pathways to convert normal stem cells into CSCs. |
Keywords | Cancer stem cells
iPSCs
Conversion
Plasticity
Tumorigenesis
Pancreatic cancer microenvironments
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Published Date | 2022-01-21
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Publication Title |
Journal Of Experimental & Clinical Cancer Research
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Volume | volume41
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Issue | issue1
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Publisher | BMC
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Start Page | 29
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ISSN | 1756-9966
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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) 2021.
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.1186/s13046-021-02167-3
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License | http://creativecommons.org/licenses/by/4.0/
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