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

Smout, Michael J., Sotillo, Javier, Laha, Thewarach, Papatpremsiri, Atiroch, 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). pp. 1-20.

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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.

Item ID: 41678
Item Type: Article (Refereed Research - C1)
Additional Information:

© 2015 Smout et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ISSN: 1553-7366
Funders: National Cancer Institute (NCI), National Institute of Allergy and Infectious Disease (NIAID), National Health and Medical Research Council (NHMRC), Queensland Government
Projects and Grants: NCI Award R01CA164719, NIAID Award P50AI098639
Date Deposited: 08 Dec 2015 14:54
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060103 Cell Development, Proliferation and Death @ 50%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 20%
11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 30%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 40%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 40%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920117 Skin and Related Disorders @ 20%
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