通过增强葡萄糖运输有关蛋白的表达,脑癌干细胞为争夺大脑内有限的营养提高了自身的竞争力。10月发表在《自然—神经科学》上的一项研究揭示了这些干细胞是如何能在营养相对缺乏的大脑中存活并繁殖的,并有助于进一步研发出针对这类癌症的疗法。
多形性胶质母细胞瘤(GBM)是成人脑肿瘤中最常见以及最致命的一种。同许多癌症一样,GBM肿瘤细胞的能量消耗也非常高。但是,这种细胞却能在大脑中有限的能量——葡萄糖的争夺中具有实力。
Jeremy Rich等人报告称,营养限制会导致一种被称为大脑肿瘤原始细胞(BITC)的肿瘤类癌症干细胞存活率上升。他们发现BITC会增加葡萄糖运输同源异构体3型(或者Glut 3)——一类让细胞更高效地摄取葡萄糖的蛋白——的表达。但是,研究人员在小鼠身上发现,如果Glut 3的表达受阻,那么BITC的生长和肿瘤繁殖将减少。此外,他们还发现Glut 3的表达水平与病患的GBM严重程度和预测有关。(生物谷Bioon.com)
生物谷推荐的英文摘要
Nature Neuroscience doi:10.1038/nn.3510
Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake
William A Flavahan, Qiulian Wu, Masahiro Hitomi, Nasiha Rahim, Youngmi Kim, Andrew E Sloan, Robert J Weil, Ichiro Nakano, Jann N Sarkaria, Brett W Stringer, Bryan W Day, Meizhang Li, Justin D Lathia, eremy N Rich & Anita B Hjelmeland
Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.