GSK-3α/β and MEK inhibitors assist the microenvironment of tumor initiation
العنوان: | GSK-3α/β and MEK inhibitors assist the microenvironment of tumor initiation |
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المؤلفون: | Ghmkin Hassan, Said M. Afify, Maram H. Zahra, Hend M. Nawara, Kazuki Kumon, Yoshiaki Iwasaki, David S. Salomon, Akimasa Seno, Masaharu Seno |
المصدر: | Cytotechnology. 75:243-253 |
بيانات النشر: | Springer Science and Business Media LLC, 2023. |
سنة النشر: | 2023 |
مصطلحات موضوعية: | Clinical Biochemistry, Biomedical Engineering, Bioengineering, Cell Biology, Biotechnology |
الوصف: | 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. |
تدمد: | 1573-0778 0920-9069 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::6ff36a9153d9a8c660271ca46a223204 https://doi.org/10.1007/s10616-023-00575-1 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi...........6ff36a9153d9a8c660271ca46a223204 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15730778 09209069 |
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