Details

Autor(en) / Beteiligte

• Bhome, Rahul
• Goh, Rebecca W
• Bullock, Marc D
• Pillar, Nir
• Thirdborough, Stephen M
• Mellone, Massimiliano
• Mirnezami, Reza
• Galea, Dieter
• Veselkov, Kirill
• Gu, Quan
• Underwood, Timothy J
• Primrose, John N
• De Wever, Olivier
• Shomron, Noam
• Sayan, A Emre
• Mirnezami, Alex H

Titel

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

Ist Teil von

• Aging (Albany, NY.), 2017-12, Vol.9 (12), p.2666-2694

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2017

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

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