Ubonrat Thamrongwaranggoon1,2, Sakkarn Sangkhamanon3, Wunchana Seubwai2,4, Paksiree Saranaruk1, Ubon Cha'on1, Sopit Wongkham5,2. 1. Department of Biochemistry, and Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 2. Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. 3. Departmemt of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 4. Department of Forensic Medicine, Faculty of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 5. Department of Biochemistry, and Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; sopit@kku.ac.th.
Abstract
BACKGROUND/AIM: Glucose transporter 1 (GLUT1) has been demonstrated to be overexpressed in various cancer tissues and play a significant role on growth, metastasis, and apoptosis in cancer cells. This study aimed to reveal the clinical relevance of glucose transporter 1 (GLUT1) in carcinogenesis and progression on liver fluke-associated cholangiocarcinoma (CCA). MATERIALS AND METHODS: Expression of GLUT1 in CCA tissues from patients, as well as from a liver fluke-induced CCA hamster model, was determined using immunohistochemistry. CCA cell lines were transfected with GLUT1 siRNA and the roles of GLUT1 on cell growth as well as migration and invasion were investigated by using a clonogenic assay and Boyden chamber assays, respectively. RESULTS: GLUT1 was aberrantly expressed in hyperplastic/dysplastic bile ducts and CCA, but not in the normal bile ducts. High GLUT1 expression was significantly associated with non-papillary type, large tumor size, and short survival of patients. GLUT1 was expressed during cholangio-carcinogenesis and gradually increased with progression of histopathologic bile ducts. Silencing of GLUT1 expression significantly suppressed growth, migration, and invasion of CCA cell lines. CONCLUSION: GLUT1 plays important roles in carcinogenesis and progression of liver fluke-associated CCA. Targeting GLUT1 may be a strategy for treatment of metastasis in liver fluke-associated CCA. Copyright
BACKGROUND/AIM: Glucose transporter 1 (GLUT1) has been demonstrated to be overexpressed in various cancer tissues and play a significant role on growth, metastasis, and apoptosis in cancer cells. This study aimed to reveal the clinical relevance of glucose transporter 1 (GLUT1) in carcinogenesis and progression on liver fluke-associated cholangiocarcinoma (CCA). MATERIALS AND METHODS: Expression of GLUT1 in CCA tissues from patients, as well as from a liver fluke-induced CCA hamster model, was determined using immunohistochemistry. CCA cell lines were transfected with GLUT1 siRNA and the roles of GLUT1 on cell growth as well as migration and invasion were investigated by using a clonogenic assay and Boyden chamber assays, respectively. RESULTS:GLUT1 was aberrantly expressed in hyperplastic/dysplastic bile ducts and CCA, but not in the normal bile ducts. High GLUT1 expression was significantly associated with non-papillary type, large tumor size, and short survival of patients. GLUT1 was expressed during cholangio-carcinogenesis and gradually increased with progression of histopathologic bile ducts. Silencing of GLUT1 expression significantly suppressed growth, migration, and invasion of CCA cell lines. CONCLUSION:GLUT1 plays important roles in carcinogenesis and progression of liver fluke-associated CCA. Targeting GLUT1 may be a strategy for treatment of metastasis in liver fluke-associated CCA. Copyright
Authors: Kátia C Carvalho; Isabela W Cunha; Rafael M Rocha; Fernanda R Ayala; Mariana M Cajaíba; Maria D Begnami; Rafael S Vilela; Geise R Paiva; Rodrigo G Andrade; Fernando A Soares Journal: Clinics (Sao Paulo) Date: 2011 Impact factor: 2.365