Analysis of interleukin-13 receptor α2 expression in human pediatric brain tumors
Analysis of interleukin-13 receptor α2 expression in human pediatric brain tumors
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DOI：
10.1002/cncr.20470
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发表时间：
2004-09-01
期刊：
影响因子：
6.2
通讯作者：
Puri, RK
中科院分区：
文献类型：
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作者：
Kawakami, M;Kawakami, K;Puri, RK
背景与正常脑组织细胞相比，人恶性胶质瘤细胞表达更高水平的白细胞介素-13受体（IL-13 R）。然而，这种受体是否在原位表达还没有仔细检查。随着IL-13 R靶向细胞毒素（IL-13-PE 38 QQR，包括IL-13和突变形式的假单胞菌外毒素[PE]）在治疗成人胶质瘤的三个I/II期临床试验中进行测试，并且计划进行儿科研究，作者着手分析儿科脑肿瘤组织标本的IL-13 R表达。采用原位杂交和免疫组化染色，作者检测了58例小儿脑肿瘤标本中主要IL-13结合和内化蛋白（IL-13 Ra 2）链在mRNA和蛋白水平的表达。总体而言，大约83%的儿科脑肿瘤样品表达IL-13 α 2。100%（11/11）的高级别星形细胞瘤、79%（26/33）的低级别星形细胞瘤、67%（4/6）的髓母细胞瘤和67%（2/3）的室管膜瘤样本均为IL-13 Ra 2阳性。在IL-13 Ra 2阳性样品中，88%（48个样品中的42个）在大于或等于50%的所有肿瘤区域中具有阳性表达。两种方法所得结果一致。目前的研究表明，小儿脑肿瘤标本表达IL-13 α 2链。由于IL-13 Ra 2链是IL-13 R复合物的主要结合组分，因此这些结果表明IL-13 R的靶向可能是治疗儿科脑肿瘤的一种有用方法。2004年由美国癌症协会出版。
BACKGROUND. Compared with normal brain tissue cells, human malignant glioma cells express higher levels of interleukin-13 receptor (IL-13R). However, whether this receptor is expressed in situ has not been carefully examined. With IL-13R-targeted cytotoxin (IL13-PE38QQR, comprising IL-13 and a mutated form of Pseudomonas exotoxin [PE]) being tested in three Phase I/II clinical trials for the treatment of adult human glioma, and with pediatric studies being planned, the authors set out to analyze pediatric brain tumor tissue specimens for the expression of IL-13R.METHODS. Using in situ hybridization and immunohistochemical staining, the authors examined 58 pediatric brain tumor specimens for expression of the predominant IL-13 binding and internalizing protein (IL-13Ralpha2) chain at the mRNA and protein levels.RESULTS. overall, approximately 83% of pediatric brain tumor samples expressed IL-13Ralpha2. One hundred percent (11 of 11) high-grade astrocytoma, 79% (26 of 33) low-grade astrocytoma, 67% (4 of 6) medulloblastoma, and 67% (2 of 3) ependymoma samples were positive for IL-13Ralpha2. Among IL-13Ralpha2-positive samples, 88% (42 of 48 samples) had positive expression in greater than or equal to 50% of all tumor fields. The results obtained using both assays were consistent with each other.CONCLUSIONS. The current study established that pediatric brain tumor specimens expressed the IL-13Ralpha2 chain. Because the IL-13Ralpha2 chain is a major binding component of the IL-13R complex, these results suggest that the targeting of IL-13R may represent a useful approach for the treatment of pediatric brain tumors. Published 2004 by the American Cancer Society.*