Debinski W, Slagle B, Gibo D M, Powers S K, Gillespie G Y
Department of Surgery, Pennsylvania State University College of Medicine, Hershey 17033-0850, USA.
J Neurooncol. 2000 Jun;48(2):103-11. doi: 10.1023/a:1006446426611.
We have previously documented that the vast majority of high-grade gliomas over-express binding sites for interleukin 13 (IL13) in situ. We now extend this analysis to evaluate the distribution of the binding of IL13 among other brain tumors. Tumor specimens from patients with low-grade gliomas, oligodendrogliomas, ependymomas, pilocytic astrocytomas, gliosarcomas, medulloblastomas, meningiomas, and metastases to the brain were analyzed and compared to a new series of glioblastoma multiforme (GBM) samples. Serial tumor tissue sections were incubated with 125I-labeled (i) IL13, (ii) antibody against transferrin (Tf) receptor, and (iii) epidermal growth factor (EGF). Most (17/18) GBMs stained specifically for IL13 binding sites while sections from 3/11 low-grade gliomas, 5/5 high-grade gliomas (grade III), 3/5 oligodendrogliomas (all three were anaplastic), and 1/2 gliosarcomas also showed specific binding for IL13. We did not detect IL13 binding sites in medulloblastomas (0/4) and found them only in 2/20 meningiomas. Metastases to the brain (4/12, i.e., lung adenocarcinomas and renal cell carcinoma) showed some binding of 125I-IL13. The presence of receptors for Tf was ubiquitous among all studied tumors while EGF receptor expression was much more variable. Since it appears that primarily the least differentiated forms of gliomas possess IL13 binding sites in abundance, it is plausible that IL 13 receptor expressed in low-grade gliomas might be a prognostically significant marker associated with their progression to high-grade gliomas. Finally, we demonstrate that the glioma-associated IL13 receptor is truly more restrictive in nature also due to its selective representation among brain tumors of glial origin.
我们之前已记录到,绝大多数高级别胶质瘤在原位过表达白细胞介素13(IL13)的结合位点。我们现在扩展该分析,以评估IL13结合在其他脑肿瘤中的分布情况。分析了来自低级别胶质瘤、少突胶质细胞瘤、室管膜瘤、毛细胞型星形细胞瘤、胶质肉瘤、髓母细胞瘤、脑膜瘤患者的肿瘤标本以及脑转移瘤,并与一系列新的多形性胶质母细胞瘤(GBM)样本进行比较。将肿瘤组织连续切片与125I标记的(i)IL13、(ii)抗转铁蛋白(Tf)受体抗体和(iii)表皮生长因子(EGF)一起孵育。大多数(17/18)GBM对IL13结合位点呈特异性染色,而3/11的低级别胶质瘤、5/5的高级别胶质瘤(III级)、3/5的少突胶质细胞瘤(均为间变性)和1/2的胶质肉瘤切片也显示出对IL13的特异性结合。我们在髓母细胞瘤中未检测到IL13结合位点(0/4),仅在2/20的脑膜瘤中发现了它们。脑转移瘤(4/12,即肺腺癌和肾细胞癌)显示出一些125I-IL13的结合。Tf受体在所有研究的肿瘤中普遍存在,而EGF受体表达则变化更大。由于似乎主要是分化程度最低的胶质瘤形式大量存在IL13结合位点,因此低级别胶质瘤中表达的IL 13受体可能是与其向高级别胶质瘤进展相关的具有预后意义的标志物,这似乎是合理的。最后,我们证明胶质瘤相关的IL13受体在本质上确实更具限制性,这也是由于其在胶质起源的脑肿瘤中的选择性表达。