a granulin-like growth factor secreted by the carcinogenic liver fluke, opisthorchis viverrini, promotes proliferation of host cells致癌的granulin-like生长因子分泌肝吸虫,opisthorchis viverrini,促进宿主细胞扩散.pdfVIP

A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells 1 2 1 3 3 4 Michael J. Smout , Thewarach Laha , Jason Mulvenna , Banchob Sripa , Sutas Suttiprapa , Alun Jones , 5 1 Paul J. Brindley , Alex Loukas * 1 Division of Infectious Diseases, Queensland Institute of Medical Research, Queensland, Australia, and School of Population Health, The University of Queensland, Queensland, Australia, 2 Department of Parasitology, Khon Kaen University, Khon Kaen, Thailand, 3 Department of Pathology, Khon Kaen University, Khon Kaen, Thailand, 4 Institute for Molecular Biosciences, The University of Queensland, Queensland, Australia, 5 Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, D. C., United States of America Abstract The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 w