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Distribution of the Glucose Transporters in Human Brain Tumors¹

Department of Neurosurgery [T. N., Y. O., H. K.], Department of Metabolism and Clinical Nutrition [Y. S., T. Y.], Second Department of Internal Medicine [N. I., H. Y., H. I.], and Department of Morphological Brain Science [R. S.], Kyoto University Medical School, Sakyo-ku, Kyoto 606, Japan

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.

¹ Supported in part by Grants in Aids for Basic Research on Radiation Therapy (03151034) and Special Project Research on Cancer Bio-Science from the Ministry of Education, Science, and Culture of Japan, by Takeda Medical Foundation, and by Monbusho International Scientific Research: Joint Research.

² To whom requests for reprints should be addressed, at Department of Neurosurgery, Kyoto University Medical School, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan.

Received 1/21/92. Accepted 5/ 5/92.

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