Santi Alice, Caselli Anna, Ranaldi Francesco, Paoli Paolo, Mugnaioni Camilla, Michelucci Elena, Cirri Paolo
Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi di Firenze, 50134 Firenze, Italy.
Mass Spectrometry Center, Università degli Studi di Firenze,, 50139 Firenze, Italy.
Biochim Biophys Acta. 2015 Dec;1853(12):3211-23. doi: 10.1016/j.bbamcr.2015.09.013. Epub 2015 Sep 16.
Fibroblasts are the most abundant cells in connective tissue and, with fibrillar extracellular matrix, form the structural scaffolding of organs. In solid tumors, interaction with cancer cells induces fibroblasts transdifferentiation into an activated form, which become a fundamental part of the tumor stroma. Within tumor microenvironment stromal and cancer cells engage a crosstalk that is mediated by soluble factors, cellcell contacts and extracellular vesicles trafficlking. Here we report that fibroblasts have the ability to transfer a remarkable amount of proteins and lipids to neighboring cells, in an ectosome-dependent fashion, identifying a novel and native property of these cells. Cancer-associated fibroblasts show an enhanced production and delivering of ectc:Jsomes to cancer cells compared to normal fibroblasts. As a consequence of this phenomenon, tumor cells increase their proliferation rate, indicating that ectosome-mediated trafficking could be a relevant mechanism mediating the trophic function of activated connective tissue on tumor cells.
成纤维细胞是结缔组织中最丰富的细胞,与纤维状细胞外基质一起构成器官的结构支架。在实体瘤中,与癌细胞的相互作用会诱导成纤维细胞转分化为活化形式,成为肿瘤基质的基本组成部分。在肿瘤微环境中,基质细胞和癌细胞通过可溶性因子、细胞间接触和细胞外囊泡运输进行相互作用。在此,我们报告成纤维细胞能够以胞外体依赖的方式将大量蛋白质和脂质转移至邻近细胞,从而确定了这些细胞的一种新的固有特性。与正常成纤维细胞相比,癌症相关成纤维细胞向癌细胞分泌和递送胞外体的能力增强。这种现象导致肿瘤细胞增殖速率增加,表明胞外体介导的运输可能是介导活化结缔组织对肿瘤细胞营养作用的一种相关机制。