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Extracellular vesicles carry microRNA-195 to intrahepatic cholangiocarcinoma and improve survival in a rat model.
Li, Ling; Piontek, Klaus; Ishida, Masaharu; Fausther, Michel; Dranoff, Jonathan A; Fu, Rongdang; Mezey, Esteban; Gould, Stephen J; Fordjour, Francis K; Meltzer, Stephen J; Sirica, Alphonse E; Selaru, Florin M.
Afiliação
  • Li L; Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, MD.
  • Piontek K; Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, MD.
  • Ishida M; Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, MD.
  • Fausther M; Department of Surgery, Tohoku University, Sendai, Japan.
  • Dranoff JA; Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR.
  • Fu R; Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR.
  • Mezey E; Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, MD.
  • Gould SJ; Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, MD.
  • Fordjour FK; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Meltzer SJ; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • Sirica AE; Division of Gastroenterology and Hepatology, School of Medicine, The Johns Hopkins University, Baltimore, MD.
  • Selaru FM; Division of Cellular and Molecular Pathogenesis, Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA.
Hepatology ; 65(2): 501-514, 2017 02.
Article em En | MEDLINE | ID: mdl-27474881
ABSTRACT
The cancer microenvironment plays a central role in cancer development, growth, and homeostasis. This paradigm suggests that cancer fibroblasts support cancers, probably in response to stimuli received from the cancer cells. We aimed at investigating whether extracellular vesicles (EVs) can shuttle microRNA (miR) species between cancer-associated fibroblasts (CAFs) and cancer cells. To this end, we extracted EVs according to published protocols. EVs were studied for their miR content by quantitative reverse-transcription polymerase chain reaction. EVs were transfected with select miR species and utilized in vitro as well as in vivo in a rat model of cholangiocarcinoma (CCA). We found that miR-195 is down-regulated in CCA cells, as well as in adjoining fibroblasts. Furthermore, we report that EVs shuttle miR-195 from fibroblasts to cancer cells. Last, we show that fibroblast-derived EVs, loaded with miR-195, can be administered in a rat model of CCA, concentrate within the tumor, decrease the size of cancers, and improve survival of treated rats.

CONCLUSION:

EVs play a salient role in trafficking miR species between cancer cells and CAFs in human CCA. Understanding of these mechanisms may allow devising of novel therapeutics. (Hepatology 2017;65501-514).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias dos Ductos Biliares / Colangiocarcinoma / MicroRNAs / Microambiente Tumoral / Vesículas Extracelulares Tipo de estudo: Clinical_trials / Diagnostic_studies / Guideline Limite: Animals / Humans / Male Idioma: En Revista: Hepatology Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Moldávia
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias dos Ductos Biliares / Colangiocarcinoma / MicroRNAs / Microambiente Tumoral / Vesículas Extracelulares Tipo de estudo: Clinical_trials / Diagnostic_studies / Guideline Limite: Animals / Humans / Male Idioma: En Revista: Hepatology Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Moldávia