Molecular Biology of Glucose Transporter expressed in Brain Tumors

脑肿瘤的生长速度与葡萄糖代谢之间可能存在密切关系，正电子发射断层扫描（PET）的临床研究表明，脑肿瘤中葡萄糖的脑代谢利用增加。由于葡萄糖通过葡萄糖转运载体蛋白（GLUT）介导的易化扩散过程转运到细胞中，因此GLUT在脑肿瘤的葡萄糖代谢中起重要作用。首先，我们检测了葡萄糖转运蛋白亚型在人脑星形细胞肿瘤中的表达，并比较了GLUT mRNA和蛋白水平与星形细胞肿瘤的组织学分级之间的关系。人类星形细胞肿瘤表达GLUT 1、GLUT 3和GLUT 4的mRNA和蛋白。其中，GLUT 3是脑肿瘤中表达的主要亚型。星形细胞肿瘤细胞的组织学分级与葡萄糖转运蛋白的表达水平无相关性。其次，我们确定了C6大鼠胶质瘤细胞的生长速度，葡萄糖转运系统和葡萄糖代谢之间的关系。将大鼠C6神经胶质瘤细胞亚克隆至4种不同的细胞系（CL 1-CL 4），其中CL 1生长缓慢，而CL 4生长迅速。与CL 1相比，CL 4中的GLUT水平和葡萄糖摄取显著增加。此外，细胞内葡萄糖和ATP的浓度也证明了快速生长细胞（CL 4）中葡萄糖代谢速率的增加。提示星形胶质细胞肿瘤细胞中易化葡萄糖转运蛋白（GLUT）可能发生改变，胶质瘤细胞的生长速度与葡萄糖转运和糖代谢密切相关。

There may be a close relationship between the growth rate of brain tumor and glucose metabolism, as clinical studies with positron emission tomography (PET) have demonstrated that cerebral metabolic ultilization of glucose is increased in brain tumors. Since the glucose is transported into the cell through a facilitated diffusion process, mediated by glucose transporter carrier protein (GLUT), GLUT must play an inportant role in glucose metabolism of a brain tumor. First of all, we have examined the expression of glucose transporter isoforms in human astrocytic tumors, and compared the levels of GLUT mRNA and protein with the histological grading of astrocytic tumor. Human astrocytic tumors expressed the mRNAs and proteins of GLUT1, GLUT3, and GLUT4. Among them, GLUT3 was the major isoform expressed in brain tumors. There was no correlation between the histological grading of human astrocytic tumor cells and the expression levels of glucose transporter. Second, we determined the relationship between the growth rate of C6 rat glioma cells, the glucose transport system, and glucose metabolism. Rat C6 glioma cells were subcloned to 4 different cell lines (CL1-CL4), where CL1 is growing slowly, and CL4 is rapidly growing. The levels of GLUT and uptake of glucose were markedly increased in CL4 compared to in CL1. Further, the concentrations of intracellular glucose and ATP also demonstrated the increased rate of glucose metabolism in the rapidly growing cells (CL4). These results suggest that the facilitative glucose transporter (GLUT) may be altered in astrocytic tumor cells and the growth rate of glioma cells is closely related to the glucose transport and glucose metabolism.