Conditioned Medium from Adipose-Derived Stem Cells (ADSCs) Promotes Epithelial-to-Mesenchymal-Like Transition (EMT-Like) in Glioma Cells In vitro
Conditioned Medium from Adipose-Derived Stem Cells (ADSCs) Promotes Epithelial-to-Mesenchymal-Like Transition (EMT-Like) in Glioma Cells In vitro
复制标题
DOI：
10.1007/s12035-015-9585-4
复制
发表时间：
2016-12-01
影响因子：
5.1
通讯作者：
Wink, Marcia R.
中科院分区：
文献类型：
--
作者：
Iser, Isabele C.;Ceschini, Stefanie M.;Wink, Marcia R.
间充质干细胞(MSCs)最近被描述为脑肿瘤的宿主，并整合到肿瘤相关的基质中。了解癌细胞和MSCs之间的交流已经成为决定MSC-肿瘤相互作用是否应该被用作治疗药物的载体或被视为干预目标的基础。因此，我们通过分析几种体外细胞生物学过程来研究脂肪干细胞条件培养液(ADSCs-CM)对胶质瘤细胞的调控作用。用ADSCs-CM处理C6大鼠脑胶质瘤细胞，分析细胞增殖、细胞周期、细胞活力、细胞形态、黏附、迁移以及上皮-间充质转化(EMT)相关表面标志的表达。ADSCs-CM不改变C6胶质瘤细胞的存活率、细胞周期和生长速度，但增加其迁移能力。此外，经ADSC-CM处理的C6细胞黏附能力降低，细胞形态发生改变。ADSC-CM治疗后也观察到EMT相关标志物(Vimentin、MMP2和NRAS)的上调。我们的研究结果表明，ADSCs释放的旁分泌因子能够调节胶质瘤细胞的生物学。因此，在设计干细胞治疗的临床应用时，必须考虑肿瘤微环境中ADSC与肿瘤细胞的相互作用。
Mesenchymal stem cells (MSCs) have recently been described to home to brain tumors and to integrate into the tumor-associated stroma. Understanding the communication between cancer cells and MSCs has become fundamental to determine whether MSC-tumor interactions should be exploited as a vehicle for therapeutic agents or considered a target for intervention. Therefore, we investigated whether conditioned medium from adipose-derived stem cells (ADSCs-CM) modulate glioma tumor cells by analyzing several cell biology processes in vitro. C6 rat glioma cells were treated with ADSCs-CM, and cell proliferation, cell cycle, cell viability, cell morphology, adhesion, migration, and expression of epithelial-mesenchymal transition (EMT)-related surface markers were analyzed. ADSCs-CM did not alter cell viability, cell cycle, and growth rate of C6 glioma cells but increased their migratory capacity. Moreover, C6 cells treated with ADSC-CM showed reduced adhesion and underwent changes in cell morphology. Up-regulation of EMT-associated markers (vimentin, MMP2, and NRAS) was also observed following treatment with ADSC-CM. Our findings demonstrate that the paracrine factors released by ADSCs are able to modulate glioma cell biology. Therefore, ADSC-tumor cell interactions in a tumor microenvironment must be considered in the design of clinical application of stem cell therapy.