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Extracellular vesicles carry microRNA-195 to intrahepatic cholangiocarcinoma and improve survival in a rat model.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2017 Feb; Vol. 65 (2), pp. 501-514. Date of Electronic Publication: 2016 Aug 29. - Publication Year :
- 2017
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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.<br />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;65:501-514).<br />Competing Interests: No authors have any potential conflicts in reference to this manuscript.<br /> (© 2016 by the American Association for the Study of Liver Diseases.)
- Subjects :
- Animals
Bile Duct Neoplasms genetics
Bile Duct Neoplasms pathology
Carcinogenesis genetics
Cell Movement genetics
Cholangiocarcinoma genetics
Cholangiocarcinoma pathology
Disease Models, Animal
Down-Regulation
Fibroblasts pathology
Humans
Immunohistochemistry
Male
MicroRNAs genetics
Random Allocation
Rats
Rats, Inbred F344
Real-Time Polymerase Chain Reaction methods
Sensitivity and Specificity
Survival Rate
Transfection
Tumor Cells, Cultured pathology
Bile Duct Neoplasms mortality
Cholangiocarcinoma mortality
Extracellular Vesicles genetics
MicroRNAs pharmacology
Tumor Microenvironment genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3350
- Volume :
- 65
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 27474881
- Full Text :
- https://doi.org/10.1002/hep.28735