Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function-猫眼课题宝

DOI：

10.1101/2023.01.13.523951

发表时间：

2023-01

期刊：

bioRxiv

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Alice Santi;Emily J. Kay;L. Neilson;L. Mcgarry;S. Lilla;Margaret Mullin;Nikki R. Paul;F. Fercoq;Grigorios Koulouras;G. R. Blanco;D. Athineos;Susan Mason;Mark Hughes;Y. Kieffer;Colin Nixon;K. Blyth;F. Mechta-Grigoriou;Leo M. Carlin;S. Zanivan

实体瘤中不同细胞类型之间的细胞间通讯有助于肿瘤的生长和转移。肿瘤相关成纤维细胞(CAF)的分泌体在这些过程中起着重要作用。利用人乳腺CAF，我们揭示了具有肌成纤维细胞表型的CAF与内皮细胞(ECs)之间基于细胞外小泡(EVS)的细胞间蛋白质转移的细胞-细胞通讯机制。CAF将蛋白质转移到内皮细胞，包括质膜受体，我们已经用基于质谱学的蛋白质组学鉴定了这种受体。使用THY1作为转移的质膜结合蛋白的例子，我们证明了CAF衍生的蛋白可以影响内皮细胞与其他类型细胞的相互作用。在这里，我们展示了CAF产生大量与基质结合的EV，这些EV在蛋白质转移中起关键作用。因此，我们的工作为进一步的研究铺平了道路，以了解CAF衍生的基质结合EV如何通过调节邻近癌症、间质和免疫细胞的功能来影响肿瘤病理。一句话总结具有肌成纤维细胞样表型的CAF通过基质结合的EVS将蛋白质转移到ECs，包括质膜受体

Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we unveil a mechanism of cell-cell communication between CAFs with myofibroblast phenotype and endothelial cells (ECs) based on intercellular protein transfer through extracellular vesicles (EVs). CAFs transfer proteins to ECs, including plasma membrane receptors, which we have identified by using mass spectrometry- based proteomics. Using THY1 as an example of transferred plasma membrane-bound protein, we show that CAF-derived proteins can influence how ECs interact with other cell types. Here, we show that CAFs produce high amounts of matrix-bound EVs that have a key role in protein transfer. Hence, our work paves the way for further studies to understand how CAF-derived matrix-bound EVs influence tumor pathology by regulating functions of neighboring cancer, stromal and immune cells. One sentence summary CAFs with a myofibroblastic-like phenotype transfer proteins to ECs, including plasma membrane receptors, through matrix-bound EVs

Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function

文献摘要

相似文献