Carcinogenic parasite secretes growth factor that accelerates wound healing and potentially promotes neoplasia

Smout, Michael J., Sotillo, Javier, Laha, Thewarach, Papatpremsiri, Atorich, Rinaldi, Gabriel, Pimenta, Rafael N., Chan, Lai Yue, Johnson, Michael S., Turnbull, Lynne, Whitchurch, Cynthia B., Giacomin, Paul R., Moran, Corey S., Golledge, Jonathan, Daly, Norelle, Sripa, Banchob, Mulvenna, Jason P., Brindley, Paul J. and Loukas, Alex (2015) Carcinogenic parasite secretes growth factor that accelerates wound healing and potentially promotes neoplasia. PLoS Pathogens, 11 10: 1-20. doi:10.1371/journal.ppat.1005209


Author Smout, Michael J.
Sotillo, Javier
Laha, Thewarach
Papatpremsiri, Atorich
Rinaldi, Gabriel
Pimenta, Rafael N.
Chan, Lai Yue
Johnson, Michael S.
Turnbull, Lynne
Whitchurch, Cynthia B.
Giacomin, Paul R.
Moran, Corey S.
Golledge, Jonathan
Daly, Norelle
Sripa, Banchob
Mulvenna, Jason P.
Brindley, Paul J.
Loukas, Alex
Title Carcinogenic parasite secretes growth factor that accelerates wound healing and potentially promotes neoplasia
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7374
Publication date 2015-10-20
Year available 2015
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1005209
Open Access Status DOI
Volume 11
Issue 10
Start page 1
End page 20
Total pages 20
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Subject 2405 Parasitology
2404 Microbiology
2403 Immunology
1312 Molecular Biology
1311 Genetics
2406 Virology
Abstract 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.
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID P50AI098639
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
 
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