Cancer-associated fibroblasts (CAFs) are one of the main components of the stromal compartment in the tumor microenvironment (TME) and the crosstalk between CAFs and cancer cells is essential for tumor progression and aggressiveness. Cancer cells mediate an activation process, converting normal fibroblasts into CAFs, that are characterized by modified expression of many proteins and increased production and release of microvesicles (MVs), extracellular vesicles generated by outwards budding from the cell membrane. Recent evidence underlined that the uptake of CAF-derived MVs changes the overall protein content of tumor cells. In this paper, we demonstrate that tumor activated fibroblasts overexpress Galectin-1 (Gal-1) and consequently release MVs containing increased levels of this protein. The uptake of Gal-1 enriched MVs by tumor cells leads to the upregulation of its intracellular concentration, that strongly affects cancer cell migration, while neither proliferation nor adhesion are altered. Accordingly, tumor cells co-cultured with fibroblasts silenced for Gal-1 have a reduced migratory ability. The present work reveals the key role of an exogenous protein, Gal-1, derived from activated fibroblasts, in cancer progression, and contributes to clarify the importance of MVs-mediated protein trafficking in regulating tumor-stroma crosstalk.

癌症相关成纤维细胞（CAF）是肿瘤微环境（TME）基质腔室的主要成分之一，并且CAF与癌细胞之间的串扰对肿瘤的进展和侵袭性至关重要。癌细胞介导激活过程，将正常的成纤维细胞转化为CAF，其特征是许多蛋白质的表达被修饰，微囊泡（MVs）的产生和释放增加，微囊泡是由细胞膜向外发芽而产生的细胞外囊泡。最近的证据强调，摄取CAF衍生的MV会改变肿瘤细胞的总蛋白质含量。在本文中，我们证明了肿瘤激活的成纤维细胞过表达Galectin-1（Gal-1），因此释放出含有增加的该蛋白水平的MV。肿瘤细胞对富含Gal-1的MV的吸收导致其细胞内浓度的上调，这强烈影响癌细胞的迁移，而增殖和粘附均未改变。因此，与针对Gal-1沉默的成纤维细胞共培养的肿瘤细胞迁移能力降低。本工作揭示了源自活化成纤维细胞的外源蛋白Gal-1在癌症进展中的关键作用，并有助于阐明MVs介导的蛋白运输在调节肿瘤基质间的串扰中的重要性。