Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression

摘要: Colorectal cancer is a global disease with increasing incidence. Mortality largely attributed to metastatic spread and therefore, mechanistic dissection of the signals which influence tumor progression needed. Cancer stroma plays critical role in proliferation, invasion chemoresistance. Here, we sought identify characterize exosomal microRNAs as mediators stromal-tumor signaling. In vitro, demonstrated that fibroblast exosomes are transferred colorectal cells, resultant increase cellular microRNA levels, impacting proliferation To probe this further, were profiled from paired patient-derived normal cancer-associated fibroblasts, an ongoing prospective biomarker study. An signature consisting 329, 181a, 199b, 382, 215 21 was identified. Of these, miR-21 had highest abundance enriched exosomes. Orthotopic xenografts established miR-21-overexpressing fibroblasts CRC cells led increased liver metastases compared those control fibroblasts. Our data provide novel stromal exosome cancer, has potential for validation. Furthermore, confirmed importance using orthotopic model, propose vehicle transfer between cells.