TY - JOUR ID - 67392 TI - Granulin Expression in Hamsters during Opisthorchis viverrini Infection-Induced Cholangiocarcinogenesis JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Upontain, Songkiad AU - Sereerak, Piya AU - Laha, Thewarach AU - Sripa, Banchob AU - Tangkawatana, Prasarn AU - Brindley, Paul J AU - Tangkawattana, Sirikachorn AD - Graduate School, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease)/Tropical Disease Research Center (TDRC), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand. AD - Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington DC 20037, USA. Y1 - 2018 PY - 2018 VL - 19 IS - 9 SP - 2437 EP - 2445 KW - cholangiocarcinoma KW - granulin KW - hamster model KW - Opisthorchis viverrini KW - carcinogenesis DO - 10.22034/APJCP.2018.19.9.2437 N2 - The secreted growth factor granulin (GRN) is upregulated during diverse epithelial cancers. GRN stimulatescell growth and development while inhibiting apoptosis. Orthologues of vertebrate granulins evolved in otheranimals including the liver fluke Opisthorchis viverrini. Curiously, liver fluke granulin, termed Ov-GRN-1 promotescholangiocarcinogenesis during chronic opisthorchiasis but, by contrast, limited information is available concerningmammalian GRN during liver fluke infection-induced cholangiocarcinoma (CCA). Here we investigated the expressionof mammalian granulin in the O. viverrini-associated a hamster model of opisthorchiasis and liver fluke infection-inducedCCA. Male Syrian golden hamsters were assigned to one of four treatment groups, each group included 30 hamsters: 1)normal (control), 2) infected with O. viverrini (OV); 3) exposed to N-dimethylnitrosamine in drinking water (DMN);and 4) infected with O. viverrini and exposed to DMN (OVDMN). Immunohistochemistry using an anti-granulinspecific probe for mammalian granulin was undertaken to monitor expression and location in hepatobiliary tissues ofthe hamsters. In parallel, cognate studies of transcription of mRNA and protein. Histopathological examination revealeddevelopment of proliferative lesions from the onset and eruption of CCA onwards, an outcome that was most prominentin the OVDMN hamsters. Proliferating cell nuclear antigen (PCNA) index rose continuously from initiation of infectionand increased with lesion progression in OV, DMN and markedly in OVDMN hamsters. Expression of GRN in biliarywas elevated in biliary epithelial cells in CCA lesions in hamsters in the DMN and OVDMN groups. Expression of GRNas assayed by western blot and RT-PCR reflected the same trend as seen with PCNA. Together the histopathogical andmolecular assay based findings revealed marked expression of granulin during cholangiocarcinoma in these hamsters,and highlighted the prospect that granulin represents a potential prognostic marker for cholangiocarcinoma. UR - https://journal.waocp.org/article_67392.html L1 - https://journal.waocp.org/article_67392_512f586308fe79d322741d94cee97985.pdf ER -