间质干细胞/基质细胞吞噬揭示乳腺癌转移优势。
Mesenchymal Stem/Stromal Cell Engulfment Reveals Metastatic Advantage in Breast Cancer.
机构信息
Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA; Forbes Institute for Cancer Discovery, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Cell Rep. 2019 Jun 25;27(13):3916-3926.e5. doi: 10.1016/j.celrep.2019.05.084.
Twenty percent of breast cancer (BC) patients develop distant metastasis for which there is no cure. Mesenchymal stem/stromal cells (MSCs) in the tumor microenvironment were shown to stimulate metastasis, but the mechanisms are unclear. Here, we identified and quantified cancer cells engulfing stromal cells in clinical samples of BC metastasis by dual immunostaining for EZH2 and ALDH1 expression. Using flow cytometry and a microfluidic single-cell paring and retrieval platform, we show that MSC engulfment capacity is associated with BC cell metastatic potential and generates cells with mesenchymal-like, invasion, and stem cell traits. Whole-transcriptome analyses of selectively retrieved engulfing BC cells identify a gene signature of MSC engulfment consisting of WNT5A, MSR1, ELMO1, IL1RL2, ZPLD1, and SIRPB1. These results delineate a mechanism by which MSCs in the tumor microenvironment promote metastasis and provide a microfluidic platform with the potential to predict BC metastasis in clinical samples.
20%的乳腺癌（BC）患者会发生远处转移，目前对此尚无治愈方法。肿瘤微环境中的间充质干细胞/基质细胞（MSCs）被证明会刺激转移，但具体机制尚不清楚。在这里，我们通过对 EZH2 和 ALDH1 表达的双重免疫染色，在 BC 转移的临床样本中鉴定和量化了癌细胞吞噬间质细胞的情况。我们使用流式细胞术和微流控单细胞配对和检索平台，表明 MSC 吞噬能力与 BC 细胞的转移潜能相关，并产生具有间充质样、侵袭和干细胞特性的细胞。对选择性回收的吞噬 BC 细胞进行全转录组分析，确定了一个由 MSC 吞噬组成的基因特征，包括 WNT5A、MSR1、ELMO1、IL1RL2、ZPLD1 和 SIRPB1。这些结果描绘了肿瘤微环境中的 MSCs 促进转移的机制，并提供了一种具有在临床样本中预测 BC 转移潜力的微流控平台。
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