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

Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Lai Yue Chan, Michael S. Johnson, Lynne Turnbull, Cynthia B. Whitchurch, Paul R. Giacomin, Corey S. Moran, Jonathan Golledge, Norelle Daly, Banchob Sripa, Jason P. Mulvenna, Paul J. Brindley, Alex Loukas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Citations (SciVal)
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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.

Original languageEnglish
Article numbere1005209
JournalPLOS Pathogens
Volume11
Issue number10
DOIs
Publication statusPublished - 20 Oct 2015
Externally publishedYes

Keywords

  • Amino Acid Sequence
  • Animals
  • Bile Duct Neoplasms/parasitology
  • Carcinogenesis/metabolism
  • Cholangiocarcinoma/parasitology
  • Helminth Proteins/metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Mice
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Opisthorchiasis/complications
  • Opisthorchis/metabolism
  • Progranulins
  • RNA Interference
  • Wound Healing/physiology

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