Carcinogenic liver fluke secretes extracellular vesicles that promote cholangiocytes to adopt a tumorigenic phenotype

Chaiyadet, Sujittra, Sotillo, Javier, Smout, Michael, Cantacessi, Cinzia, Jones, Malcolm K., Johnson, Michael S., Turnbull, Lynne, Whitchurch, Cynthia B., Potriquet, Jeremy, Laohaviroj, Marut, Mulvenna, Jason, Brindley, Paul J., Bethony, Jeffrey M., Laha, Thewarach, Sripa, Banchob and Loukas, Alex (2015) Carcinogenic liver fluke secretes extracellular vesicles that promote cholangiocytes to adopt a tumorigenic phenotype. Journal of Infectious Diseases, 212 10: 1636-1645. doi:10.1093/infdis/jiv291


Author Chaiyadet, Sujittra
Sotillo, Javier
Smout, Michael
Cantacessi, Cinzia
Jones, Malcolm K.
Johnson, Michael S.
Turnbull, Lynne
Whitchurch, Cynthia B.
Potriquet, Jeremy
Laohaviroj, Marut
Mulvenna, Jason
Brindley, Paul J.
Bethony, Jeffrey M.
Laha, Thewarach
Sripa, Banchob
Loukas, Alex
Title Carcinogenic liver fluke secretes extracellular vesicles that promote cholangiocytes to adopt a tumorigenic phenotype
Journal name Journal of Infectious Diseases   Check publisher's open access policy
ISSN 0022-1899
1537-6613
Publication date 2015-11-15
Sub-type Article (original research)
DOI 10.1093/infdis/jiv291
Open Access Status DOI
Volume 212
Issue 10
Start page 1636
End page 1645
Total pages 10
Place of publication Cary, NC, United States
Publisher Oxford University Press
Language eng
Formatted abstract
Background:  Throughout Asia, there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes, including chronic inflammation and secretion of parasite proteins into the biliary epithelium, drive infection toward cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

Methods:  Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterized the EV proteome and associated changes in cholangiocytes after EV uptake, and we detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and interleukin 6 (IL-6) secretion was measured to assess the impact of EV internalization.

Results:  EVs were identified in fluke culture medium and bile specimens from infected hosts. EVs internalized by cholangiocytes drove cell proliferation and IL-6 secretion and induced changes in protein expression associated with endocytosis, wound repair, and cancer. Antibodies to an O. viverrini tetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes.

Conclusions:  This is the first time that EVs from a multicellular pathogen have been identified in host tissues. Our findings imply a role for O. viverrini EVs in pathogenesis and highlight an approach to vaccine development for this infectious cancer.
Keyword extracellular vesicles
Opisthorchis viverrini
Cholangiocarcinoma
Liver fluke
Cancer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Veterinary Science Publications
 
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