A granulin growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, and its role in wound healing and carcinogenesis

MJ Smout1,2, J Sotillo1,2, P Giacomin1,2, L Thewarch3, P Brindley4, G Rinaldi4 and AC Loukas1,2

  1. James Cook University (JCU) - Cairns
  2. Australian Institute of Tropical Health and Medicine (AITHM)
  3. Khon Kaen University - Khon Kaen, Thailand
  4. George Washington University, Washington DC, USA

Parasitic worms are large, invasive pathogens. To combat the pathology they induce, worms evolved strategies to promote wound repair in infected hosts. The Thai liver fluke, Opisthorchis viverrini, induces such extensive immunopathology and protracted wound healing that it causes cancer. We show that the secreted proteins of O. viverrini accelerated wound repair in human cholangiocytes, and this repair process was diminished by silencing expression in the fluke-of a gene that encodes for the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated wound healing in mice. Ov-GRN-1 was internalized by cholangiocytes and induced changes in expression of proteins and mRNAs associated with wound healing and cancer pathways. This is the first description of a pathogen protein that stimulates wound repair and in doing so contributes to the establishment of a tumorigenic environment. Ov-GRN-1 holds promise as both a novel wound healing agent and vaccine with anti-parasitic and anti-cancer properties.