Dourado Mauricio Rocha, Korvala Johanna, Åström Pirjo, De Oliveira Carine Ervolino, Cervigne Nilva K, Mofatto Luciana Souto, Campanella Bastos Debora, Pereira Messetti Ana Camila, Graner Edgard, Paes Leme Adriana Franco, Coletta Ricardo D, Salo Tuula
Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.
Cancer and Translational Medicine Research Unit, Faculty of Medicine and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.
J Extracell Vesicles. 2019 Feb 13;8(1):1578525. doi: 10.1080/20013078.2019.1578525. eCollection 2019.
As one of the most abundant constituents of the tumour microenvironment (TME), cancer-associated fibroblasts (CAF) display critical roles during tumour progression and metastasis. Multiple classes of molecules including growth factors, cytokines, proteases and extracellular matrix proteins, are produced by CAF to act as mediators of the stroma-tumour interactions. One of the main channels for this communication is associated with extracellular vesicles (EV), which are secreted particles loaded with protein and genetic information. In this study, we evaluated the effects of EV derived from CAF primary human cell lines (n = 5) on proliferation, survival, migration, and invasion of oral squamous cell carcinoma (OSCC) cells. As controls, EV from human primary-established normal oral fibroblasts (NOF, n = 5) were used. Our assays showed that CAF-EV significantly induces migration and invasion of OSCC cells and promote a disseminated pattern of HSC-3 cell invasion in the 3D organotypic assay. Furthermore, gene expression analysis of EV-treated cancer cells revealed changes in the pathways associated with tumour metabolism and up-regulation of tumour invasion genes. Our findings suggest a significant role of CAF-EV in promoting the migration and invasion of OSCC cells, which are related to the activation of cancer-related pathways.
作为肿瘤微环境（TME）中最丰富的成分之一，癌症相关成纤维细胞（CAF）在肿瘤进展和转移过程中发挥着关键作用。CAF可产生多种分子，包括生长因子、细胞因子、蛋白酶和细胞外基质蛋白，作为基质与肿瘤相互作用的介质。这种通讯的主要渠道之一与细胞外囊泡（EV）有关，细胞外囊泡是装载蛋白质和遗传信息的分泌颗粒。在本研究中，我们评估了源自CAF原代人细胞系（n = 5）的EV对口腔鳞状细胞癌（OSCC）细胞增殖、存活、迁移和侵袭的影响。作为对照，使用了源自人原代建立的正常口腔成纤维细胞（NOF，n = 5）的EV。我们的实验表明，CAF-EV在三维器官型实验中显著诱导OSCC细胞的迁移和侵袭，并促进HSC-3细胞侵袭的播散模式。此外，对经EV处理的癌细胞的基因表达分析揭示了与肿瘤代谢相关的通路变化以及肿瘤侵袭基因的上调。我们的研究结果表明，CAF-EV在促进OSCC细胞的迁移和侵袭中起重要作用，这与癌症相关通路的激活有关。
