Correlation between bradykinin-induced blood-tumor barrier permeability and B2 receptor expression in experimental brain tumors
Correlation between bradykinin-induced blood-tumor barrier permeability and B2 receptor expression in experimental brain tumors
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DOI：
10.1179/016164101101198596
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发表时间：
2001-06-01
影响因子：
1.9
通讯作者：
Black, KL
中科院分区：
文献类型：
--
作者：
Liu, YH;Hashizume, K;Black, KL
本研究通过检测脑肿瘤细胞和脑肿瘤微血管内皮细胞B2受体的定位，探讨脑肿瘤对缓激肽的敏感性差异。目前的研究表明，B2受体表达水平在培养的RG 2，C6和9 L胶质瘤细胞以及在脑内肿瘤建立与这些细胞系在大鼠。双重免疫组化数据表明，B2受体定位于肿瘤细胞，而不是肿瘤毛细血管。免疫组化和Western blot分析显示，B2受体的表达顺序为C6 > RG 2> 9 L。对大鼠RG 2、C6和9 L肿瘤的渗透性研究表明，颈动脉内输注缓激肽后，C6肿瘤的Ki（单向转运穿过血脑屏障（BBB）/血肿瘤屏障（BTB））增加最多（178%），而9 L肿瘤的Ki增加最少（35%）。我们发现B2受体水平与缓激肽诱导的BTB通透性增加呈正相关（r=0.965，p < 0.001）。我们的结论是，B2受体定位于肿瘤细胞，而不是正常或肿瘤毛细血管内皮细胞。具有最高B2受体表达的C6肿瘤对缓激肽最敏感，而具有较低B2受体表达水平的RG 2和9 L肿瘤在BTB渗透性方面对缓激肽不太敏感。
Localization of B2 receptors in brain tumor cells and microvessel endothelial cells of the brain tumors was investigated to study the differential sensitivity of brain tumors to bradykinin. The present study shows that B2 receptor expression levels vary in cultured RG2, C6 and 9L glioma cells as well as in the intracerebral tumors established with these cell lines in rats. The double immunohistochemical data indicate that B2 receptors are localized to tumor cells and not to the tumor capillaries. Immunostaining and Western blot analysis for B2 receptor showed that the B2 receptor expression was in the order C6 > RG2 > 9L. The permeability studies on RG2, C6 and 9L tumors in rats showed that C6 tumor had the highest increase (178%) in K-i (unidirectional transport across blood-brain barrier (BBB)/blood-tumor barrier (BTB)), while 9L tumor had the least increase of K-i (35%) over the control group, following intracarotid infusion of bradykinin. We found a positive correlation (r=0.965, p < 0.001) between B2 receptor levels and bradykinin-induced increase in BTB permeability. We conclude that B2 receptors are localized to tumor cells and not to normal or tumor capillary endothelial cells. C6 tumor with highest B2 receptor expression was most responsive to bradykinin, while RG2 and 9L tumors with lower B2 receptor expression level were less sensitive to bradykinin with regard to BTB permeability.