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

Bhome, R. et al. (2017) Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression. Aging, 9(12), pp. 2666-2694. (doi: 10.18632/aging.101355) (PMID:29283887)

Abstract

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. In vitro, 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.

• Item Type: Articles
• Additional Information: Funding: Cancer Research UK Pre-Doctoral Bursary (A20526) and Clinical Research Training Fellowship awarded to RB. British Council UK-Israel Nanoscience Fellowship awarded to RB. MRC (RCUK/UKRI) Clinical Research Training Fellowship (MR/R002061/1) awarded to RB. MRC Clinical Research Training Fellowship awarded to MB. Wessex Medical Research Innovation Grants awarded to AES and AHM.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gu, Dr Quan
• Authors: Bhome, R., Goh, R., Bullock, M., Pillar, N., Thirdborough, S., Mellone, M., Mirnezami, R., Galea, D., Veselkov, K., Gu, Q., Underwood, T., Primrose, J., Wever, O., Shomron, N., Sayan, A. E., and Mirnezami, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Aging
• Publisher: Impact Journals
• ISSN: 1945-4589
• ISSN (Online): 1945-4589
• Published Online: 28 December 2017
• Copyright Holders: Copyright © 2017 Bohme et al.
• First Published: First published in Aging 9(12): 2666-2694
• Publisher Policy: Reproduced under a Creative Commons License