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.;Loukas, Alex

Paul Giacomin Jonathan Golledge

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.

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PLoS Pathogens

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1553-7366

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PLOS

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DOI

10.1371/journal.ppat.1005209