The research deals with cholangiocarcinoma (CCA), bile duct cancer, caused by infection with the liver fluke, Opisthorchis viverrini. CCA is a primary cancer originating in the epithelium (cholangiocytes) ofthe bile ducts. It has long latency, is invasive, metastasizes and has a dismal prognosis. The mechanisms by which chronic infection with the flukes results in CCA are likely multi-factorial, but one mechanism is the secretion of parasite proteins with mitogenic and anti-apoptotic properties, both features of a pre-cancerous cellular environment. We have characterised the excretory/secretory (ES) products of O. viverrini and identified two candidate ES proteins that are central to these processes - we showed that a homologue of the human secreted growth factor, granulin, binds to cholangiocytes and stimulates proliferation of fibroblasts and CCA cell lines. We also showed that secreted thioredoxin peroxidase blocks apoptosis of damaged cholangiocytes. Progression of chronic opisthorchiasis to CCA follows a multi-factorial route(s). We hypothesize that key processes along the route include (1) secretion of parasite proteins which induce pathology in the biliary tract and establish an environment conducive to cancer development by promoting cell proliferation and DNA damage, accelerating wound healing and blocking apoptosis;and (2) repeated administration of the anthelmintic drug praziquantel, for treatment of O. viverrini (Ov) infection, causes increased inflammation in the bile ducts and thereby precipitates tumorigenesis. The research will investigate these phenomena by assessing the ability of Ov-ES to (1) facilitate wound repair in mammalian cells;(2) promote cell invasion and migration;(3) interfere with apoptosis. To further address the carcinogenic roles of these proteins, we will vaccinate hamsters with Ov-ES and its defined components to determine whether this intervention can protect against liver fluke infection and CCA, and assessment of impact of repeated PZQ therapy in accelerating tumorigenesis.
Despite treatment and health education campaigns, the prevalence of O. viverrini infection remains high in Northeast Thailand;more problematically, infection with O. viverrini often leads to a deadly form of liver cancer. The work proposed here investigates - at the molecular level - how liver fluke infection causes this liver cancer, and could offer new strategies to control this disease.
|Surapaitoon, Arpa; Suttiprapa, Sutas; Khuntikeo, Narong et al. (2017) Cytokine profiles in Opisthorchis viverrini stimulated peripheral blood mononuclear cells from cholangiocarcinoma patients. Parasitol Int 66:889-892|
|Potriquet, Jeremy; Laohaviroj, Marut; Bethony, Jeffrey M et al. (2017) A modified FASP protocol for high-throughput preparation of protein samples for mass spectrometry. PLoS One 12:e0175967|
|Chaiyadet, Sujittra; Smout, Michael; Laha, Thewarach et al. (2017) Proteomic characterization of the internalization of Opisthorchis viverrini excretory/secretory products in human cells. Parasitol Int 66:494-502|
|Deenonpoe, Raksawan; Mairiang, Eimorn; Mairiang, Pisaln et al. (2017) Elevated prevalence of Helicobacter species and virulence factors in opisthorchiasis and associated hepatobiliary disease. Sci Rep 7:42744|
|van Tong, Hoang; Brindley, Paul J; Meyer, Christian G et al. (2017) Parasite Infection, Carcinogenesis and Human Malignancy. EBioMedicine 15:12-23|
|Sripa, Banchob; Deenonpoe, Raksawan; Brindley, Paul J (2017) Co-infections with liver fluke and Helicobacter species: A paradigm change in pathogenesis of opisthorchiasis and cholangiocarcinoma? Parasitol Int 66:383-389|
|Kim, Christina Sunyoung; Smith, John F; Suwannatrai, Apiporn et al. (2017) Role of socio-cultural and economic factors in cyprinid fish distribution networks and consumption in Lawa Lake region, Northeast Thailand: Novel perspectives on Opisthorchis viverrini transmission dynamics. Acta Trop 170:85-94|
|Echaubard, Pierre; León, Tomas; Suwanatrai, Kulwadee et al. (2017) Experimental and modelling investigations of Opisthorchis viverrini miracidia transmission over time and across temperatures: implications for control. Int J Parasitol 47:257-270|
|Vinh, Hoang Quang; Phimpraphai, Waraphon; Tangkawattana, Sirikachorn et al. (2017) Risk factors for Clonorchis sinensis infection transmission in humans in northern Vietnam: A descriptive and social network analysis study. Parasitol Int 66:74-82|
|Van, Chinh Dang; Doungchawee, Galayanee; Suttiprapa, Sutas et al. (2017) Association between Opisthorchis viverrini and Leptospira spp. infection in endemic Northeast Thailand. Parasitol Int 66:503-509|
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