Takano S, Yoshii Y, Kondo S, Suzuki H, Maruno T, Shirai S, Nose T
Department of Neurosurgery, Soujinkai Hospital, Ibaraki, Japan.
Cancer Res. 1996 May 1;56(9):2185-90.
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. 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.
血管内皮生长因子（VEGF）已被作为脑肿瘤血管生成、血管通透性和胶质瘤生长的一种强效介质进行研究。我们使用VEGF酶联免疫吸附测定法（ELISA），测定了19例脑肿瘤患者血清和肿瘤提取物中的VEGF浓度，这些患者包括胶质母细胞瘤、间变性星形细胞瘤、低级别星形细胞瘤、脑膜瘤、恶性淋巴瘤和转移性脑肿瘤患者以及正常脑组织患者。虽然血清中的VEGF浓度与组织中的VEGF浓度不相关，但胶质母细胞瘤囊液中的VEGF浓度比患者血清中的VEGF浓度高200 - 300倍。肿瘤中的VEGF浓度与通过计数用血管性血友病因子抗体染色的血管所测量的血管密度显著相关。VEGF蛋白定位于胶质瘤中肿瘤细胞和脉管系统的细胞质中，主要定位于外周微血管“热点”以及胶质母细胞瘤坏死灶周围。VEGF免疫阳性与ELISA测定的VEGF浓度密切相关。VEGF ELISA显示各种胶质瘤细胞系的无血清条件培养基中VEGF浓度呈时间依赖性增加。高VEGF浓度的条件培养基诱导内皮细胞迁移。这些观察结果表明，VEGF是胶质母细胞瘤血管生成的一个有用标志物和可测量指标。通过ELISA测定肿瘤和肿瘤囊液中的VEGF浓度可能有助于评估胶质瘤中的血管密度。
