| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
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.
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