Nishioka T, Oda Y, Seino Y, Yamamoto T, Inagaki N, Yano H, Imura H, Shigemoto R, Kikuchi H
Department of Neurosurgery, Kyoto University Medical School, Japan.
Cancer Res. 1992 Jul 15;52(14):3972-9.
In the present study, we have investigated the expression of both the erythrocyte-type (GLUT1) and the brain-type (GLUT3) glucose transporter isoforms in primary human brain tumors. In situ hybridization made it possible to localize and semiquantify both GLUT1 and GLUT3 mRNAs of individual cells in all 18 samples examined. More signals for GLUT3 mRNA than for GLUT1 mRNA were found over astrocytoma cells, while the reverse was the case in all 6 meningiomas. In astrocytomas, for both mRNAs, the density of silver grains over tumor cells was well correlated with the malignancy of the cells. This correlation was, as was also confirmed by Northern blot analysis, more marked with GLUT3 mRNA than with GLUT1 mRNA. In 2 of 5 anaplastic astrocytomas and in all 3 glioblastomas, numerous tumor cells with large amounts of both mRNAs tended to surround the perivascular regions. "Tumor vessels" with endothelial proliferation, an almost pathognomonic feature of glioblastomas, expressed much GLUT3 mRNA but no significant GLUT1 mRNA, while a single- or a few-layered capillary endothelium expressed much GLUT1 mRNA. The distribution of both mRNAs was in good accordance with that of both proteins. Our results suggest that the expression of both glucose transporter isoforms may contribute to the maintenance of human brain tumors and that the expression of the GLUT3 isoform may be closely related to the malignant change of astrocytomas and particularly related to the aberrant neovascularization which accompanies glioblastomas.
在本研究中，我们调查了原代人脑肿瘤中红细胞型（GLUT1）和脑型（GLUT3）葡萄糖转运蛋白异构体的表达情况。原位杂交使我们能够在所有18个检测样本中定位并半定量单个细胞的GLUT1和GLUT3 mRNA。在星形细胞瘤细胞上发现的GLUT3 mRNA信号比GLUT1 mRNA信号更多，而在所有6例脑膜瘤中情况则相反。在星形细胞瘤中，对于这两种mRNA，肿瘤细胞上银颗粒的密度与细胞的恶性程度密切相关。正如Northern印迹分析所证实的那样，这种相关性在GLUT3 mRNA上比在GLUT1 mRNA上更为明显。在5例间变性星形细胞瘤中的2例以及所有3例胶质母细胞瘤中，大量表达这两种mRNA的肿瘤细胞倾向于围绕血管周围区域。具有内皮细胞增殖的“肿瘤血管”是胶质母细胞瘤几乎具有诊断意义的特征，其表达大量GLUT3 mRNA但无明显的GLUT1 mRNA，而单层或几层的毛细血管内皮细胞则表达大量GLUT1 mRNA。这两种mRNA的分布与两种蛋白质的分布高度一致。我们的结果表明，两种葡萄糖转运蛋白异构体的表达可能有助于维持人脑肿瘤，并且GLUT3异构体的表达可能与星形细胞瘤的恶性变化密切相关，尤其与伴随胶质母细胞瘤的异常新生血管形成有关。
