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A microfluidic chip for screening individual cancer cells via eavesdropping on autophagyinducing crosstalk in the stroma niche

机译:通过窃听基质噬菌体中自噬诱导的串扰来筛选单个癌细胞的微流控芯片

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摘要

Autophagy is a cellular homeostatic mechanism where proteins and organelles are digested and recycled to provide an alternative source of building blocks and energy to cells. The role of autophagy in cancer microenvironment is still poorly understood. Here, we present a microfluidic system allowing monitoring of the crosstalk between single cells. We used this system to study how tumor cells induced autophagy in the stromal niche. Firstly, we could confirm that transforming growth factor beta 1 (TGF beta 1) secreted from breast tumor cells is a paracrine mediator of tumor-stroma interaction leading to the activation of autophagy in the stroma component fibroblasts. Through proof of concept experiments using TGF beta 1 as a model factor, we could demonstrate real time monitoring of autophagy induction in fibroblasts by single tumor cells. Retrieval of individual tumor cells from the microfluidic system and their subsequent genomic analysis was possible, allowing us to determine the nature of the factor mediating tumor-stroma interactions. Therefore, our microfluidic platform might be used as a promising tool for quantitative investigation of tumor-stroma interactions, especially for and high-throughput screening of paracrine factors that are secreted from heterogeneous tumor cell populations.
机译:自噬是一种细胞内稳态机制,其中蛋白质和细胞器被消化并循环利用,从而为细胞提供替代的结构单元和能量来源。自噬在癌症微环境中的作用仍然知之甚少。在这里,我们介绍了一种微流体系统,可以监控单个细胞之间的串扰。我们使用该系统来研究肿瘤细胞如何诱导基质位中的自噬。首先,我们可以确认从乳腺肿瘤细胞分泌的转化生长因子β1(TGFβ1)是肿瘤-基质相互作用的旁分泌介质,导致基质成分成纤维细胞中自噬的激活。通过使用TGF beta 1作为模型因子的概念验证实验,我们可以证明对单个肿瘤细胞在成纤维细胞中自噬诱导的实时监控。从微流体系统中检索单个肿瘤细胞及其后续的基因组分析是可能的,这使我们能够确定介导肿瘤-基质相互作用的因子的性质。因此,我们的微流控平台可以用作定量研究肿瘤-基质相互作用的有前途的工具,特别是用于高通量筛选异种肿瘤细胞群体分泌的旁分泌因子。

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