title: Proteomic characterization of the internalization of Opisthorchis viverrini excretory/secretory products in human cells.
abstract: The association between liver fluke infection caused by Opisthorchis viverrini and cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium) has been well established. Multiple mechanisms play a role in the development of CCA, but the excretory/secretory products released by O. viverrini (OvES) represent the major interface between the parasite and its host, and their uptake by biliary epithelial cells has been suggested to be responsible for proliferation of cholangiocytes, the cells that line the biliary epithelium. Despite recent progress in the study of the molecular basis of O. viverrini-host interactions, little is known about the effects that OvES induces upon internalization by host cells. In the present study we incubated non-cancerous human cholangiocytes (H69) and human colon cancer (CaCo-2) cells with OvES and performed a time-course quantitative proteomic analysis on the cells to determine the early changes induced by the parasite. Different KEGG pathways were altered in H69 cells compared to Caco-2 cells: glycolysis/gluconeogenesis and protein processing in the endoplasmic reticulum. In addition, the Reactome pathway analysis showed a predominance of proteins involved in cellular pathways related to apoptosis and apoptotic execution phase in H69 cells after incubation with OvES. The present study provides the first proteomic analysis to address the molecular mechanisms by which OvES products interact with host cells, and Sheds light on the cellular processes involved in O. viverrini-induced CCA.
authors.affiliation: Biomedical Sciences, Graduate School, Khon Kaen University, Khon Kaen, Thailand; Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors.forename: Sujittra
authors.initials: S
authors.lastname: Chaiyadet
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Smout
authors.affiliation: Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Thewarach
authors.initials: T
authors.lastname: Laha
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia. Electronic address: javier.sotillo@jcu.edu.au.
authors.forename: Javier
authors.initials: J
authors.lastname: Sotillo
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000469:parasitology*; D018938:Caco-2 Cells; D018281:Cholangiocarcinoma / Q000469:parasitology*; D004847:Epithelial Cells; D015801:Helminth Proteins / Q000378:metabolism*; D006801:Humans; D009889:Opisthorchiasis / Q000150:complications / Q000378:metabolism* / Q000469:parasitology; D009891:Opisthorchis / Q000502:physiology*; D020543:Proteome
chemical_list: D015801:Helminth Proteins; D020543:Proteome
keywords: Caco-2 cells; Cholangiocytes; Excretory/secretory products; Opisthorchis viverrini; Proteomics; iTRAQ