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

PLoS Pathogens

Paul R. Giacomin¹  Banchob Sripa¹  Michael J. Smout¹  Javier Sotillo¹  Rafael N. Pimenta²  Alex Loukas²  Gabriel Rinaldi²  Atiroch Papatpremsiri³  Thewarach Laha³  Jason P. Mulvenna⁴  Norelle Daly⁵  Michael S. Johnson⁶  Lynne Turnbull⁶  Cynthia B. Whitchurch⁶  Paul J. Brindley⁷  Jonathan Golledge⁸  Corey S. Moran⁸  Lai Yue Chan⁹ 

[1] Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia;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;Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;Department of Pathology, Khon Kaen University, Khon Kaen, Thailand;Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia;Microbial Imaging Facility, The iThree institute, University of Technology Sydney, Ultimo, New South Wales, Australia;QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia;Queensland Research Centre for Peripheral Vascular Disease, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia;The Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia

关键词: Wound healing;    Growth factors;    Gene expression;    Parasitic diseases;    Cell proliferation;    Recombinant proteins;    Protein expression;    Tissue repair;   

DOI  :  10.1371/journal.ppat.1005209

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY