Mesenchymal stroma/stem-like cells (MSCs) have antitumour activity, and MSC-derived exosomes play a role in the growth, metastasis and invasion of tumour cells. Additionally, glycoprotein A repetition predominant (GARP) promotes oncogenesis in breast cancer. Therefore, GARP is speculated to be a target gene for cancer therapy. We aimed to explore the therapy role of MSC-derived exosomes targeting GARP in mouse colon cancer cell MC38. We successfully established a GARP knockdown system using three kinds of siRNA-GARP in MSC cells. Exosomes were isolated from MSC and siGARP-MSC cells, and verified by the exosome surface protein markers CD9, CD63 and CD81. GARP expression was significantly decreased in siGARP-MSC exosomes compared with that of MSC exosomes. We found that siGARP-MSC exosomes inhibited cell proliferation, migration and invasion of MC38 cells, using CCK-8, colony formation, wound-healing and Transwell invasion assays. Furthermore, siGARP-MSC exosomes impeded IL-6 secretion and partly inactivated JAK1/STAT3 pathway, measured using ELISA and RT-qPCR. In conclusion, MSC-derived exosomes targeting GARP are a potential strategy for cancer therapy.
Keywords: GARP; IL-6; JAK1/STAT3 pathway; MC38 cells; MSC; cancer therapy; cell proliferation; exosome; invasion; migration.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.