PMID- 27474881
OWN - NLM
STAT- MEDLINE
DCOM- 20170807
LR  - 20181113
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 65
IP  - 2
DP  - 2017 Feb
TI  - Extracellular vesicles carry microRNA-195 to intrahepatic cholangiocarcinoma and 
      improve survival in a rat model.
PG  - 501-514
LID - 10.1002/hep.28735 [doi]
AB  - 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;65:501-514).
CI  - (c) 2016 by the American Association for the Study of Liver Diseases.
FAU - Li, Ling
AU  - Li L
AD  - Division of Gastroenterology and Hepatology, School of Medicine, The Johns 
      Hopkins University, Baltimore, MD.
FAU - Piontek, Klaus
AU  - Piontek K
AD  - Division of Gastroenterology and Hepatology, School of Medicine, The Johns 
      Hopkins University, Baltimore, MD.
FAU - Ishida, Masaharu
AU  - Ishida M
AD  - Division of Gastroenterology and Hepatology, School of Medicine, The Johns 
      Hopkins University, Baltimore, MD.
AD  - Department of Surgery, Tohoku University, Sendai, Japan.
FAU - Fausther, Michel
AU  - Fausther M
AD  - Division of Gastroenterology and Hepatology, University of Arkansas for Medical 
      Sciences, Little Rock, AR.
FAU - Dranoff, Jonathan A
AU  - Dranoff JA
AD  - Division of Gastroenterology and Hepatology, University of Arkansas for Medical 
      Sciences, Little Rock, AR.
FAU - Fu, Rongdang
AU  - Fu R
AD  - Division of Gastroenterology and Hepatology, School of Medicine, The Johns 
      Hopkins University, Baltimore, MD.
FAU - Mezey, Esteban
AU  - Mezey E
AD  - Division of Gastroenterology and Hepatology, School of Medicine, The Johns 
      Hopkins University, Baltimore, MD.
FAU - Gould, Stephen J
AU  - Gould SJ
AD  - Department of Biological Chemistry, The Johns Hopkins University School of 
      Medicine, Baltimore, MD.
FAU - Fordjour, Francis K
AU  - Fordjour FK
AD  - Department of Biological Chemistry, The Johns Hopkins University School of 
      Medicine, Baltimore, MD.
FAU - Meltzer, Stephen J
AU  - Meltzer SJ
AD  - Division of Gastroenterology and Hepatology, School of Medicine, The Johns 
      Hopkins University, Baltimore, MD.
FAU - Sirica, Alphonse E
AU  - Sirica AE
AD  - Division of Cellular and Molecular Pathogenesis, Department of Pathology, 
      Virginia Commonwealth University School of Medicine, Richmond, VA.
FAU - Selaru, Florin M
AU  - Selaru FM
AD  - Division of Gastroenterology and Hepatology, School of Medicine, The Johns 
      Hopkins University, Baltimore, MD.
AD  - Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, MD.
AD  - The Institute for Nanobiotechnology, The Johns Hopkins University, Baltimore, MD.
LA  - eng
GR  - R01 DK076735/DK/NIDDK NIH HHS/United States
GR  - P30 DK089502/DK/NIDDK NIH HHS/United States
GR  - R01 CA083650/CA/NCI NIH HHS/United States
GR  - K08 DK090154/DK/NIDDK NIH HHS/United States
GR  - R56 DK070849/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20160829
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (MicroRNAs)
SB  - IM
CIN - Hepatology. 2017 Feb;65(2):404-406. PMID: 28012192
MH  - Animals
MH  - Bile Duct Neoplasms/genetics/*mortality/pathology
MH  - Carcinogenesis/genetics
MH  - Cell Movement/genetics
MH  - Cholangiocarcinoma/genetics/*mortality/pathology
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Extracellular Vesicles/*genetics
MH  - Fibroblasts/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - MicroRNAs/genetics/*pharmacology
MH  - Random Allocation
MH  - Rats
MH  - Rats, Inbred F344
MH  - Real-Time Polymerase Chain Reaction/methods
MH  - Sensitivity and Specificity
MH  - Survival Rate
MH  - Transfection
MH  - Tumor Cells, Cultured/pathology
MH  - Tumor Microenvironment/*genetics
PMC - PMC5258762
MID - NIHMS807328
COIS- No authors have any potential conflicts in reference to this manuscript.
EDAT- 2016/07/31 06:00
MHDA- 2017/08/08 06:00
PMCR- 2018/02/01
CRDT- 2016/07/31 06:00
PHST- 2016/01/11 00:00 [received]
PHST- 2016/06/16 00:00 [revised]
PHST- 2016/07/14 00:00 [accepted]
PHST- 2016/07/31 06:00 [pubmed]
PHST- 2017/08/08 06:00 [medline]
PHST- 2016/07/31 06:00 [entrez]
PHST- 2018/02/01 00:00 [pmc-release]
AID - 10.1002/hep.28735 [doi]
PST - ppublish
SO  - Hepatology. 2017 Feb;65(2):501-514. doi: 10.1002/hep.28735. Epub 2016 Aug 29.