CD90low glioma-associated mesenchymal stromal/stem cells promote temozolomide resistance by activating FOXS1-mediated epithelial-mesenchymal transition in glioma cells

作者：Bingzhou Xue, Wei Xiang, Qing Zhang, Haofei Wang, Yujie Zhou, Han Tian, Ahmed Abdelmaksou, Jian Xue, Minxuan Sun, Dongye Yi, Nanxiang Xiong, Xiaobing Jiang, Hongyang Zhao, Peng Fu · 发表于：Stem Cell Research & Therapy · 年份：2021 · DOI：10.1186/s13287-021-02458-8 · 被引用次数：43 · 研究领域：FOXO transcription factor regulation、Cancer Cells and Metastasis、Glioma Diagnosis and Treatment

Abstract Background The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. Methods Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. Results Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EM...