Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia

Smout, MJ; Sotillo, J; Laha, T; Papatpremsiri, A; Rinaldi, G; Pimenta, RN; Chan, LY; Johnson, MS; Turnbull, L; Whitchurch, CB; Giacomin, PR; Moran, CS; Golledge, J; Daly, N; Sripa, B; Mulvenna, JP; Brindley, PJ; Loukas, A

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia

Smout, MJ Sotillo, J Laha, T Papatpremsiri, A Rinaldi, G Pimenta, RN Chan, LY Johnson, MS Turnbull, L

Whitchurch, CB

Giacomin, PR Moran, CS Golledge, J Daly, N Sripa, B Mulvenna, JP Brindley, PJ Loukas, A

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Publication Type:: Journal Article
Citation:: PLoS Pathogens, 2015, 11 (10)
Issue Date:: 2015-01-01

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Field	Value	Language
dc.contributor.author	Smout, MJ	en_US
dc.contributor.author	Sotillo, J	en_US
dc.contributor.author	Laha, T	en_US
dc.contributor.author	Papatpremsiri, A	en_US
dc.contributor.author	Rinaldi, G	en_US
dc.contributor.author	Pimenta, RN	en_US
dc.contributor.author	Chan, LY	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	Giacomin, PR	en_US
dc.contributor.author	Moran, CS	en_US
dc.contributor.author	Golledge, J	en_US
dc.contributor.author	Daly, N	en_US
dc.contributor.author	Sripa, B	en_US
dc.contributor.author	Mulvenna, JP	en_US
dc.contributor.author	Brindley, PJ	en_US
dc.contributor.author	Loukas, A	en_US
dc.date.available	2015-09-15	en_US
dc.date.issued	2015-01-01	en_US
dc.identifier.citation	PLoS Pathogens, 2015, 11 (10)	en_US
dc.identifier.issn	1553-7366	en_US
dc.identifier.uri	http://hdl.handle.net/10453/41108
dc.description.abstract	© 2015 Smout et al. Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world.	en_US
dc.relation	http://purl.org/au-research/grants/arc/LE0989920
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT0571905
dc.relation.ispartof	PLoS Pathogens	en_US
dc.relation.isbasedon	10.1371/journal.ppat.1005209	en_US
dc.subject.classification	Virology	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Opisthorchis	en_US
dc.subject.mesh	Opisthorchiasis	en_US
dc.subject.mesh	Cholangiocarcinoma	en_US
dc.subject.mesh	Bile Duct Neoplasms	en_US
dc.subject.mesh	Intercellular Signaling Peptides and Proteins	en_US
dc.subject.mesh	Helminth Proteins	en_US
dc.subject.mesh	Microscopy, Confocal	en_US
dc.subject.mesh	Oligonucleotide Array Sequence Analysis	en_US
dc.subject.mesh	Wound Healing	en_US
dc.subject.mesh	RNA Interference	en_US
dc.subject.mesh	Amino Acid Sequence	en_US
dc.subject.mesh	Molecular Sequence Data	en_US
dc.subject.mesh	Carcinogenesis	en_US
dc.subject.mesh	Progranulins	en_US
dc.title	Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	11	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1107 Immunology	en_US
utslib.for	1108 Medical Microbiology	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	11	en_US

Abstract:

© 2015 Smout et al. Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world.

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

http://hdl.handle.net/10453/41108