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@article{Bhome:2017:10.18632/aging.101355,
author = {Bhome, R and Goh, RW and Bullock, MD and Pillar, N and Thirdborough, SM and Mellone, M and Mirnezami, R and Galea, D and Veselkov, K and Gu, Q and Underwood, TJ and Primrose, JN and De, Wever O and Shomron, N and Sayan, AE and Mirnezami, AH},
doi = {10.18632/aging.101355},
journal = {Aging-US},
pages = {2666--2694},
title = {Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression},
url = {http://dx.doi.org/10.18632/aging.101355},
volume = {9},
year = {2017}
}

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TY  - JOUR
AB  - 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.
AU  - Bhome,R
AU  - Goh,RW
AU  - Bullock,MD
AU  - Pillar,N
AU  - Thirdborough,SM
AU  - Mellone,M
AU  - Mirnezami,R
AU  - Galea,D
AU  - Veselkov,K
AU  - Gu,Q
AU  - Underwood,TJ
AU  - Primrose,JN
AU  - De,Wever O
AU  - Shomron,N
AU  - Sayan,AE
AU  - Mirnezami,AH
DO  - 10.18632/aging.101355
EP  - 2694
PY  - 2017///
SN  - 1945-4589
SP  - 2666
TI  - Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression
T2  - Aging-US
UR  - http://dx.doi.org/10.18632/aging.101355
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000418910700022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/57238
VL  - 9
ER  -

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