Receptors for Growth Factors in Capillaries Isolated from Human Glioblastomas and Meningiomas

从人胶质母细胞瘤和脑膜瘤中分离出的毛细血管中生长因子的受体

• 批准号: 06671401
• 负责人: NIWA Masami
• 金额: $ 1.15万
• 依托单位: NAGASAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671401/
• 关键词: Brain Tumor; Radioluminographic imaging plate system; Quantitative receptor autoradiography; Growth factor receptors; Glioblastoma; Meningioma; Brain tumor capillary; Growth factors; radioluminographic imaging plate system; glioblastoma; meningi

We identified and characterized ^<125>I-endothelin-1 (^<125>I-ET-1) and ^<125>I-vascular endothelial growth factor (^<125>I-VEGF) binding sites in tumor capillaries isolated from human glioblastomas and meningiomas, using the quantitative receptor autoradiographic technique with pellet sections. Quantification was done using the computerized radioluminographic imaging system. High-affinity ET system receptors were localized in capillaries from glioblastomas (Kd=0.47<plus-minus>0.01 nM,Bmax=161<plus-minus>38 fmol/mg, mean<plus-minus>SEM,n=5) and the surrounding brain tissues (Kd=0.16<plus-minus>0.03nM,Bmax=140<plus-minus>37 fmol/mg, n=5). The ET_A receptor occupied 70 and 55% and the ET_B receptor occupied 30 and 45% of the binding to capillaries from glioblastomas and brains, respectively. In cases of capillaries from meningiomas, there were relatively low-affinity binding sites of ^<125>I-ET-1 with a Kd of 1.2<plus-minus>0.3 nM and Bmax of 185<plus-minus>56 fmol/mg (n=9). Capillaries in human meningiomas expressed a large number of the ET_A receptor with a small proportion of the ET_B receptor. We also detected a high-affinity binding of ^<125>I-VEGF to capillaries from glioblastomas, a candidate of VEGF receptors. Our results suggest that ET and VEGF have a role in neovascularization, tumor blood flow, and/or function of the blood-tumor barrier in meningioma and blioblastoma tissues by interacting with specific receptors present on the surface of the endothelium.

我们用定量受体放射自显影技术和颗粒切片鉴定并表征了从人胶质母细胞瘤和脑膜瘤分离的肿瘤毛细血管中的^<125>I-内皮素-1（^<125>I-ET-1）和^<125>I-血管内皮生长因子（^<125>I-VEGF）结合位点。使用计算机化放射发光成像系统进行定量。高亲和力ET系统受体定位于胶质母细胞瘤毛细血管（Kd=0.47 <plus-minus>± 0.01 nM，Bmax=161 <plus-minus>38 fmol/mg，平均<plus-minus>SEM，n=5）和周围脑组织（Kd=0.16 <plus-minus>± 0.03 nM，Bmax =140 <plus-minus>37 fmol/mg，n=5）。ET_A受体占胶质母细胞瘤和脑毛细血管的70%和55%，ET_B受体占30%和45%。在脑膜瘤毛细血管的情况下，有相对较低的亲和力结合位点的^<125>I-ET-1的Kd为1.2 - <plus-minus>0.3 nM和Bmax为185 <plus-minus>- 56 fmol/mg（n=9）。脑膜瘤中内皮素A受体大量表达，而内皮素B受体表达较少。我们还检测到一个高亲和力的结合，<125>从胶质母细胞瘤，一个候选的VEGF受体的毛细血管的^ I-VEGF。我们的研究结果表明，内皮素和血管内皮生长因子有一个新血管形成的作用，肿瘤血流，和/或功能的血肿瘤屏障脑膜瘤和成血管细胞瘤组织通过相互作用与特定的受体存在于内皮细胞表面。

项目成果

堤 圭介: "脳腫瘍の微小血管における増殖因子受容体の定量化" 神経免疫研究. 7. 43-51 (1994)

Keisuke Tsutsumi：“脑肿瘤微血管中生长因子受体的定量”神经免疫学研究。7. 43-51 (1994)。

Keisuke Tsutsumi et al.: "Enhanced expression of an endothelin ET_A receptor in capillaries from human glioblastoma : A quantitative receptor autoradiographic analysis using a radioluminographic imaging plate system" Journal of Neurochemistry. 63. 2240-22

Keisuke Tsutsumi 等人：“人胶质母细胞瘤毛细血管中内皮素 ET_A 受体的增强表达：使用放射发光成像板系统进行定量受体放射自显影分析”《神经化学杂志》。

Keisuke Tsutsumi: "Effects of suramin on ^<125>I-insulin-like growth factor I binding to human meningiomas and inhibits proliferation of meningioma cells" Journal of Neurosurgery. 80. 502-509 (1994)

Keisuke Tsutsumi：“苏拉明对^ 125 I-胰岛素样生长因子I与人脑膜瘤结合并抑制脑膜瘤细胞增殖的影响”神经外科杂志。

Naoki Kitagawa et al.: "A selective endothelin ET_A antagonist BQ-123 inhibits ^<125>I-endothelin-1 (ET-1) binding to human meningiomas antagonizes ET-1-induced proliferation of meningioma cells" Cellular and Molecular Neurobiology. 14. 105-118 (1994)

Naoki Kitakawa 等人：“选择性内皮素 ET_A 拮抗剂 BQ-123 抑制 125 I-内皮素-1 (ET-1) 与人脑膜瘤的结合，拮抗 ET-1 诱导的脑膜瘤细胞增殖”《细胞和分子神经生物学》。

Masami Niwa: "Quantitative receptor autoradiography" Folia Pharmacologica Japonica. 103. 151-160 (1994)

Masami Niwa：“定量受体放射自显影”Folia Pharmacologica Japonica。