GSK-3α/β and MEK inhibitors assist the microenvironment of tumor initiation.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2023-06-01 Epub Date: 2023-04-01 DOI:10.1007/s10616-023-00575-1
Ghmkin Hassan, Said M Afify, Maram H Zahra, Hend M Nawara, Kazuki Kumon, Yoshiaki Iwasaki, David S Salomon, Akimasa Seno, Masaharu Seno
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引用次数: 0

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.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-023-00575-1.

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GSK-3α/β和MEK抑制剂有助于肿瘤发生的微环境。
诱导多能干细胞(iPSC)是建模疾病和开发个性化药物的有用工具。我们一直在用癌症衍生细胞的条件培养基(CM)从iPSC中开发癌症干细胞(CSC),以模仿肿瘤发生的微环境。然而,仅使用CM对人iPSC的转化并不总是有效的。在本研究中,从健康志愿者的单核细胞重编程的人iPSC在含有50%来自补充有MEK抑制剂(AZD6244)和GSK-3α/β抑制剂(CHIR99021)的人胰腺癌症衍生的BxPC3细胞的CM的培养基中培养。对存活的细胞在体外和体内评估CSCs的特征。结果,它们表现出自我更新、分化和恶性致瘤性的CSC表型。转化细胞的恶性肿瘤的原代培养显示CSC相关基因CD44、CD24和EPCAM的表达升高,维持干性基因的表达。总之,GSK-3α/β和MEK的抑制作用以及CM模拟的肿瘤起始微环境可以将人类正常干细胞转化为CSCs。这项研究可以为建立潜在的新型个性化癌症模型提供见解,这有助于研究CSC的肿瘤起始和个性化治疗的筛选。补充信息:在线版本包含补充材料,可在10.1007/s10616-023-00575-1上获得。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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