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

Chaiyadet, S; Sotillo, J; Smout, M; Cantacessi, C; Jones, MK; Johnson, MS; Turnbull, L; Whitchurch, CB; Potriquet, J; Laohaviroj, M; Mulvenna, J; Brindley, PJ; Bethony, JM; Laha, T; Sripa, B; Loukas, A

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

Chaiyadet, S Sotillo, J Smout, M Cantacessi, C Jones, MK Johnson, MS Turnbull, L

Whitchurch, CB

Potriquet, J Laohaviroj, M Mulvenna, J Brindley, PJ Bethony, JM Laha, T Sripa, B Loukas, A

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Publication Type:: Journal Article
Citation:: Journal of Infectious Diseases, 2015, 212 (10), pp. 1636 - 1645
Issue Date:: 2015-11-15

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Field	Value	Language
dc.contributor.author	Chaiyadet, S	en_US
dc.contributor.author	Sotillo, J	en_US
dc.contributor.author	Smout, M	en_US
dc.contributor.author	Cantacessi, C	en_US
dc.contributor.author	Jones, MK	en_US
dc.contributor.author	Johnson, MS	en_US
dc.contributor.author	Turnbull, L https://orcid.org/0000-0002-9255-9033	en_US
dc.contributor.author	Whitchurch, CB https://orcid.org/0000-0003-2296-3791	en_US
dc.contributor.author	Potriquet, J	en_US
dc.contributor.author	Laohaviroj, M	en_US
dc.contributor.author	Mulvenna, J	en_US
dc.contributor.author	Brindley, PJ	en_US
dc.contributor.author	Bethony, JM	en_US
dc.contributor.author	Laha, T	en_US
dc.contributor.author	Sripa, B	en_US
dc.contributor.author	Loukas, A	en_US
dc.date.available	2020-05-25T19:06:43Z
dc.date.issued	2015-11-15	en_US
dc.identifier.citation	Journal of Infectious Diseases, 2015, 212 (10), pp. 1636 - 1645	en_US
dc.identifier.issn	0022-1899	en_US
dc.identifier.uri	http://hdl.handle.net/10453/38120
dc.description.abstract	© The Author 2015. 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.	en_US
dc.relation	http://purl.org/au-research/grants/arc/LE0989920
dc.relation.ispartof	Journal of Infectious Diseases	en_US
dc.relation.isbasedon	10.1093/infdis/jiv291	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.mesh	Epithelial Cells	en_US
dc.subject.mesh	Bile	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Opisthorchis	en_US
dc.subject.mesh	Opisthorchiasis	en_US
dc.subject.mesh	Cell Transformation, Neoplastic	en_US
dc.subject.mesh	Proteome	en_US
dc.subject.mesh	Microscopy	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Endocytosis	en_US
dc.subject.mesh	Phenotype	en_US
dc.subject.mesh	Cricetinae	en_US
dc.subject.mesh	Mass Spectrometry	en_US
dc.subject.mesh	Extracellular Vesicles	en_US
dc.title	Carcinogenic liver fluke secretes extracellular vesicles that promote cholangiocytes to adopt a tumorigenic phenotype	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	212	en_US
utslib.for	110309 Infectious Diseases	en_US
utslib.for	060501 Bacteriology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	open_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	212	en_US

Abstract:

© The Author 2015. 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/38120