Cancer Associated Fibroblasts-Derived Exosomes Contribute To Radioresistance Through Promoting Colorectal Cancer Stem Cells Phenotype

Purpose: Radioresistance observed in patients with colorectal cancer(CRC) may be related to the presence of cancer stem cells(CSCs) but the underlying mechanism(s) remain unclear. Cancer-associated fibroblasts(CAFs) can regulate the stemness of cancer cells and tumor radiosensitivity. In addition, exosomes have been reported to modify treatment response by mediating cell–cell communication. In this study, we aimed to investigate whether exosomes derived from CAFs(CAF-exosomes) are involved in mediating resistance to radiotherapy in colorectal cancer and to explore the underlying mechanism.methods: CSCs were isolated from the CRC cell line SW620 based on expression of CD133. The radiation sensitivity of SW620 cells treated with CAF conditioned medium(CM) or CAF-exosomes was examined in vitro and in vivo.Results: CSCs were found to be inherently resistant to cell death induced by radiotherapy. CAF-derived CM promoted clonogenicity and radioresistance of CRC cells. Further investigations revealed that exosomes isolated from CM induced the above effects whereas exosome-depleted CM(solution) was not able to induce clonogenicity and radioresistance.Conclusion: CAFs promote stemness of CRC cells and thus increase radiation resistance. Exosomes derived from CAFs play a crucial role in this process.