Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression.
Aging (Albany NY)
; 9(12): 2666-2694, 2017 12 28.
Article
em En
| MEDLINE
| ID: mdl-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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MicroRNAs
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Exossomos
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Fibroblastos Associados a Câncer
Tipo de estudo:
Risk_factors_studies
Limite:
Aged
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Aging (Albany NY)
Assunto da revista:
GERIATRIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Reino Unido