Exosomes derived from colon cancer cells promote tumour progression by affecting the tumour microenvironment

Abstract

Cancer cell-derived exosomes deliver oncogenic factors to other cells and their tumour microenvironment. We aimed to investigate the role of cancer cell-derived exosomes in colon cancer. Exosomes were isolated from colon cancer cell lines HT-29, SW480, and LoVo. Subsequently, HT-29 cells were treated with these exosomes to evaluate the effect of exosomes on cancer progression. MTT and wound-healing assays were performed to evaluate the effect of exosomes on cellular viability and migration. Moreover, we obtained cancer-associated fibroblasts (CAFs) from patients with colorectal cancer to analyse the effects of cancer cell-derived exosomes on the tumour microenvironment. We performed RNA sequencing to evaluate changes in the mRNA components of the CAFs after exosome treatment. Compared with control cells, exosome-treated cells showed significantly increased proliferation. Regarding western blotting for epithelial-mesenchymal transition markers, exosome-treated cells showed N-cadherin upregulation followed by E-cadherin downregulation. In the wound-healing assay, exosome-treated cells exhibited increased mobile properties. Additionally, exosome-treated CAFs showed increased downregulated genes. In the functional enrichment analysis, exosomes derived from each cell affected different gene regulation pathways. Our findings suggest that cancer cell-derived exosomes are crucially involved in tumour progression and metastasis by affecting the tumour microenvironment.