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Extracellular vesicles carry micro RNA ‐195 to intrahepatic cholangiocarcinoma and improve survival in a rat model
Author(s) -
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.
Publication year - 2017
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.28735
Subject(s) - microrna , extracellular vesicles , cancer cell , cancer , cancer associated fibroblasts , cancer research , biology , hepatology , transfection , fibroblast , tumor microenvironment , in vitro , microbiology and biotechnology , medicine , cell culture , gene , biochemistry , genetics
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. (H epatology 2017;65:501‐514).