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

(2017) AGING-US. 9(12). p.2666-2694
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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.
Keywords
cancer-associated fibroblasts, exosomes, microRNA, stroma, colorectal cancer, TOTAL MESORECTAL EXCISION, BREAST-CANCER, GASTROINTESTINAL CANCER, TUMOR MICROENVIRONMENT, STROMAL MYOFIBROBLASTS, DOWN-REGULATION, BLADDER-CANCER, RECTAL-CANCER, UP-REGULATION, CELLS

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Chicago
Bhome, Rahul, Rebecca W Goh, Marc D Bullock, Nir Pillar, Stephen M Thirdborough, Massimiliano Mellone, Reza Mirnezami, et al. 2017. “Exosomal microRNAs Derived from Colorectal Cancer-associated Fibroblasts : Role in Driving Cancer Progression.” Aging-us 9 (12): 2666–2694.
APA
Bhome, R., Goh, R. W., Bullock, M. D., Pillar, N., Thirdborough, S. M., Mellone, M., Mirnezami, R., et al. (2017). Exosomal microRNAs derived from colorectal cancer-associated fibroblasts : role in driving cancer progression. AGING-US, 9(12), 2666–2694.
Vancouver
1.
Bhome R, Goh RW, Bullock MD, Pillar N, Thirdborough SM, Mellone M, et al. Exosomal microRNAs derived from colorectal cancer-associated fibroblasts : role in driving cancer progression. AGING-US. 2017;9(12):2666–94.
MLA
Bhome, Rahul, Rebecca W Goh, Marc D Bullock, et al. “Exosomal microRNAs Derived from Colorectal Cancer-associated Fibroblasts : Role in Driving Cancer Progression.” AGING-US 9.12 (2017): 2666–2694. Print.
@article{8572205,
  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.},
  author       = {Bhome, Rahul and Goh, Rebecca W and Bullock, Marc D and Pillar, Nir and Thirdborough, Stephen M and Mellone, Massimiliano and Mirnezami, Reza and Galea, Dieter and Veselkov, Kirill and Gu, Quan and Underwood, Timothy J and Primrose, John N and De Wever, Olivier and Shomron, Noam and Sayan, A Emre and Mirnezami, Alex H},
  issn         = {1945-4589},
  journal      = {AGING-US},
  language     = {eng},
  number       = {12},
  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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