Cutaneous squamous cell carcinoma-derived extracellular vesicles exert an oncogenic role by activating cancer-associated fibroblasts

In this study, we investigated extracellular vesicle (EVs)-mediated intercellular communication between cutaneous squamous cell carcinoma (cSCC) cells and surrounding stroma cells in tumor microenvironment (TME). Interfering with capacity of cSCC cells to secrete EVs resulted by depletion of RAB27A inhibits cSCC tumor growth in vivo.Transcriptome analysis of tumor xenografts by RNA-seq enabling the identification of both human and mouse transcripts revealed wide-spread changes both in mouse and human cells. Impaired EV-production prominently altered the phenotype of stomal cells, in particular genes related to extracellular matrix (ECM)-formation and epithelial-mesenchymal transition (EMT). This was paralleled by transcriptomic changes in the human tumor cells showing signs of activated p53 pathway and cell apoptosis. Comparative gene expression profiling analysis of RNA-seq data for mouse xenografts generated by RAB27A-knockdown cutaneous squamous cell carcinoma cells (UT-SCC7) and mouse xenografts generated by control cells.