de Bont Judith M, van Doorn Jaap, Reddingius Roel E, Graat Gerard H M, Passier Monique M C J, den Boer Monique L, Pieters Rob
Department of Pediatric Oncology and Hematology, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
Int J Cancer. 2008 Aug 1;123(3):594-600. doi: 10.1002/ijc.23558.
The insulin-like growth factor (IGF) system plays an important role in neuronal development and may contribute to the development of brain tumors. In this study, we studied mRNA expression levels of IGFs, insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factor receptors (IGFRs) in 27 pediatric medulloblastomas, 13 pediatric ependymomas and 5 control cerebella. Compared to normal cerebellum, mRNA levels of IGFBP-2 and IGFBP-3 were significantly increased in medulloblastomas and ependymomas. IGFBP-2 expression was indicative of poor prognosis in medulloblastomas, whereas IGFBP-3 mRNA levels were especially high in anaplastic ependymomas. IGFBP-5 and IGF-II mRNA levels were significantly increased in ependymomas compared to control cerebellum. Protein expression levels of IGFs and IGFBPs were analyzed in the cerebrospinal fluid (CSF) of 16 medulloblastoma, 4 ependymoma and 23 control patients by radioimmuno assay to determine whether they could be used as markers for residual disease after surgery. No aberrant CSF protein expression levels were found for ependymoma patients. In medulloblastoma patients, the IGFBP-3 protein levels were significantly higher than in ependymoma patients and controls. Moreover, enhanced levels of proteolytic fragments of IGFBP-3 were found in the CSF of medulloblastoma patients, being in concordance with a significantly increased IGFBP-3 proteolytic activity in the CSF of these patients. In conclusion, our data suggest that the IGF system is of importance in pediatric medulloblastomas and ependymomas. Larger studies should be conducted to validate the predictive values of the levels of intact IGFBP-3 and proteolytic fragments in CSF in the follow-up of medulloblastomas.
胰岛素样生长因子（IGF）系统在神经元发育中起重要作用，可能与脑肿瘤的发生发展有关。在本研究中，我们检测了27例小儿髓母细胞瘤、13例小儿室管膜瘤和5例对照小脑组织中IGF、胰岛素样生长因子结合蛋白（IGFBP）和胰岛素样生长因子受体（IGFR）的mRNA表达水平。与正常小脑相比，髓母细胞瘤和室管膜瘤中IGFBP-2和IGFBP-3的mRNA水平显著升高。IGFBP-2的表达提示髓母细胞瘤预后不良，而间变性室管膜瘤中IGFBP-3的mRNA水平尤其高。与对照小脑相比，室管膜瘤中IGFBP-5和IGF-II的mRNA水平显著升高。通过放射免疫分析检测了16例髓母细胞瘤、4例室管膜瘤和23例对照患者脑脊液（CSF）中IGF和IGFBP的蛋白表达水平，以确定它们是否可作为术后残留疾病的标志物。室管膜瘤患者未发现CSF蛋白表达异常。髓母细胞瘤患者的IGFBP-3蛋白水平显著高于室管膜瘤患者和对照。此外，在髓母细胞瘤患者的CSF中发现IGFBP-3的蛋白水解片段水平升高，与这些患者CSF中IGFBP-3蛋白水解活性显著增加一致。总之，我们的数据表明IGF系统在小儿髓母细胞瘤和室管膜瘤中具有重要意义。应进行更大规模的研究以验证CSF中完整IGFBP-3和蛋白水解片段水平在髓母细胞瘤随访中的预测价值。
