Department of Biochemistry, and Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.
In Vivo. 2021 Jan-Feb;35(1):267-274. doi: 10.21873/invivo.12255.
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).
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.
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.
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.
背景/目的:葡萄糖转运蛋白 1(GLUT1)在各种癌症组织中过度表达,并在癌细胞的生长、转移和凋亡中发挥重要作用。本研究旨在揭示葡萄糖转运蛋白 1(GLUT1)在与肝吸虫相关的胆管癌(CCA)发生和进展中的临床相关性。
使用免疫组织化学法检测患者和肝吸虫诱导的 CCA 仓鼠模型中 CCA 组织中 GLUT1 的表达。用 GLUT1 siRNA 转染 CCA 细胞系,通过集落形成实验和 Boyden 室实验分别研究 GLUT1 对细胞生长以及迁移和侵袭的作用。
GLUT1 在增生/发育不良胆管和 CCA 中异常表达,但在正常胆管中不表达。高 GLUT1 表达与非乳头型、大肿瘤大小和患者生存期短显著相关。GLUT1 在胆管癌发生过程中表达,并随着组织病理学胆管的进展逐渐增加。沉默 GLUT1 表达显著抑制 CCA 细胞系的生长、迁移和侵袭。
GLUT1 在与肝吸虫相关的 CCA 的发生和进展中发挥重要作用。靶向 GLUT1 可能是治疗与肝吸虫相关的 CCA 转移的一种策略。