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Concentration of Vascular Endothelial Growth Factor in the Serum and Tumor Tissue of Brain Tumor Patients¹

Department of Neurosurgery, Soujinkai Hospital, 1467 Oka, Fujishiro, Kitasoumagun, Ibaraki 300-15 [S. T., T. M., S. S.]; Division of Neurological Surgery, Tsukuba University School of Medicine, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305 [Y. Y., T. N.]; and Tsukuba Research Laboratory, Toagosei Co., Ltd., 2 Ohkubo, Tsukuba, Ibaraki 300-33 [S. K., H. S.], Japan

Vascular endothelial growth factor (VEGF) has been investigated as a potent mediator of brain tumor angiogenesis, vascular permeability, and glioma growth. Using a VEGF ELISA, we determined the concentration of VEGF in the sera and tumor extracts of 19 brain tumor patients including glioblastoma, anaplastic astrocytoma, low grade astrocytoma, meningioma, malignant lymphoma, and metastatic brain tumor as well as normal brain. VEGF concentration in the tissue of glioblastomas was significantly higher than that in other types of tumors as well as normal brain. Although VEGF concentration of the serum was not correlated with that of the tissue, VEGF concentrations of glioblastoma cyst fluid were 200–300-fold higher than those of serum in the patients. VEGF concentration in the tumors was significantly correlated with the vascularity measured by counting vessels stained with von Willebrand factor antibody. VEGF protein localized to the cytoplasm of tumor cells and vasculature in gliomas, predominantly in the peripheral microvessel "hot spots" as well as around the necrosis in glioblastomas. VEGF immunopositivities were well reflected with VEGF concentration determined by ELISA. VEGF ELISA demonstrated time-dependent increase of the VEGF concentration in the serum-free conditioned medium of various glioma cell lines. The conditioned medium with high VEGF concentration induced endothelial cell migration. These observations suggest that VEGF represents a useful marker and measurable element of glioblastoma angiogenesis. The measurement of VEGF concentration by ELISA in tumor and tumor cyst fluid may allow for the assessment of vascularity in gliomas.

¹ This work was supported in part by Grant-in-Aid 06671372 from the Japanese Ministry of Education, Science, and Culture (to Y. Y.).

² To whom requests for reprints should be addressed.

Received 9/12/95. Accepted 3/ 1/95.

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