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PLoS Pathog. 2015 Oct 20;11(10):e1005209. doi: 10.1371/journal.ppat.1005209. eCollection 2015 Oct.

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

Author information

1
Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
2
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
3
Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, George Washington University, Washington, D.C., United States of America.
4
The Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
5
Microbial Imaging Facility, The iThree institute, University of Technology Sydney, Ultimo, New South Wales, Australia.
6
Queensland Research Centre for Peripheral Vascular Disease, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
7
Queensland Research Centre for Peripheral Vascular Disease, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia; Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia.
8
Department of Pathology, Khon Kaen University, Khon Kaen, Thailand.
9
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

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.

PMID:
26485648
PMCID:
PMC4618121
DOI:
10.1371/journal.ppat.1005209
[Indexed for MEDLINE]
Free PMC Article

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