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Irradiated mesenchymal stem cells support stemness maintenance of hepatocellular carcinoma stem cells through Wnt/β-catenin signaling pathway.
Cell and Bioscience ( IF 6.1 ) Pub Date : 2020-08-03 , DOI: 10.1186/s13578-020-00449-5
Jing Hou 1 , Naping Zhao 2 , Pengxi Zhu 3 , Jun Chang 1 , Yan Du 1 , Wei Shen 1
Affiliation  

Cancer stem cells are the main reason of relapse, metastasis and resistance to anti-cancer therapies of Hepatocellular carcinoma (HCC). Mesenchymal stem cells (MSCs) are an important part of the tumor microenvironment. MSCs have been demonstrated to be involved in drug resistance in tumor. How MSCs contribute to radiotherapy resistance of HCC is still indistinct. Flow cytometry analysis was performed to isolate CD133+ cells from HCC cell lines Huh7 and PLC. The stemness of Huh7-CD133 and PLC-CD133 those were co-cultured with IR-MSCs were investigated by Colony formation assay. Tumor formation in nude mice was used to explore the tumorigenicity of CD133+ cancer cells. The activating Wnt/β-catenin signaling pathway in CSCs were also detected by RT-PCR and Western blotting. We report that irradiated MSCs (IR-MSCs) could increase the ratio of CD133+ cells in hepatocellular carcinoma cells. IR-MSCs could promote stemness maintenance of HCC stem cells. After co-cultured with IR-MSCs, liver cancer stem cells (CSCs) presented increased colony formation ability and tumor formation ability. We also found IR-MSCs promoted Wnt expression of CSCs. Reverse suppression experiment showed that when Wnt inhibitor was added into the culture medium, the effect of IR-MSCs on stemness maintenance was counteracted. These data showed that IR-MSCs could support stemness maintenance of CSCs by activating Wnt/β-catenin signaling pathway.

中文翻译:

辐照间充质干细胞通过 Wnt/β-catenin 信号通路支持肝细胞癌干细胞的干性维持。

肿瘤干细胞是肝细胞癌(HCC)复发、转移和抗癌治疗耐药的主要原因。间充质干细胞(MSCs)是肿瘤微环境的重要组成部分。MSCs已被证明与肿瘤的耐药性有关。间充质干细胞如何促进 HCC 的放射治疗抗性仍不清楚。进行流式细胞术分析以从 HCC 细胞系 Huh7 和 PLC 中分离 CD133+ 细胞。通过菌落形成试验研究了与IR-MSCs共培养的Huh7-CD133和PLC-CD133的干性。裸鼠中的肿瘤形成用于探索 CD133+ 癌细胞的致瘤性。还通过 RT-PCR 和蛋白质印迹检测了 CSCs 中激活的 Wnt/β-catenin 信号通路。我们报告照射的 MSCs (IR-MSCs) 可以增加肝细胞癌细胞中 CD133+ 细胞的比例。IR-MSCs可以促进HCC干细胞的干性维持。与 IR-MSCs 共培养后,肝癌干细胞 (CSCs) 的集落形成能力和肿瘤形成能力增强。我们还发现 IR-MSCs 促进了 CSCs 的 Wnt 表达。反向抑制实验表明,当培养基中加入Wnt抑制剂时,IR-MSCs对干性维持的影响被抵消。这些数据表明,IR-MSCs 可以通过激活 Wnt/β-catenin 信号通路来支持 CSCs 的干性维持。肝癌干细胞(CSCs)的集落形成能力和肿瘤形成能力增强。我们还发现 IR-MSCs 促进了 CSCs 的 Wnt 表达。反向抑制实验表明,当培养基中加入Wnt抑制剂时,IR-MSCs对干性维持的影响被抵消。这些数据表明,IR-MSCs 可以通过激活 Wnt/β-catenin 信号通路来支持 CSCs 的干性维持。肝癌干细胞(CSCs)的集落形成能力和肿瘤形成能力增强。我们还发现 IR-MSCs 促进了 CSCs 的 Wnt 表达。反向抑制实验表明,当培养基中加入Wnt抑制剂时,IR-MSCs对干性维持的影响被抵消。这些数据表明,IR-MSCs 可以通过激活 Wnt/β-catenin 信号通路来支持 CSCs 的干性维持。
更新日期:2020-08-03
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