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Neurotrophin Receptor Expression in Primitive Neuroectodermal Tumors of the Brain in Childhood

儿童脑部原始神经外胚层肿瘤中神经营养蛋白受体的表达

基本信息

批准号：
07457308
负责人：
WASHIYAMA Kazuo
金额：
$ 3.97万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

Primitive neuroectodermal tumor (PNET) of the Central Nervous System are poorly understood childhood neoplasms, and medulloblastomas are the most common pediatric PNETs. Neoplastic Cells in medulloblastomas and other PNETs resemble progenitor cells of the developing central nervous system, but they also may exhibit the molecular phenotype of immature neurons or glia.As neurotrophins play a role in regulating differentiation, proliferation, and cell death in the normal developing central nervous system, and recent evidence suggests that neurotrophins may influence the behavior of medulloblastomas, we studied 29 PNET biopsy samples (27 of which were posterior fossa medulloblastomas) by immunohistochemisty using antibodies specific for each of the major high affinity neurotrophin receptor proteins, ie, TrkA,and TrkC.A subset of these tumors also was examined by Western blot. Immunoreactive TrkA,TrkB,and TrkC were observed in neoplastic cells in 20%, 50% of these PNETs, respectively. TrkA and TrkB were mainly observed in follicular structures, and TrkC was observed in undifferentiated tumor cells, not in follicular structures. Additional immunohistochemical studies of a subset of these PNETs using antibodies to neurotrophins that primarily activate TrkB and TrkC,ie, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5, showed that immunoreactive brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 were detected in 20,10, and 20% of these PNET biopsies, respectively.The demonstration here that neurotrophins and their cognate receptor proteins are expressed in PNETs may immply that signal transduction pathways mediated by neurotrophins and/or their receptors influence the induction or progression of these common childhood neoplasms.

中枢神经系统原始神经外胚层肿瘤(PNET)是一种少见的儿童肿瘤，髓母细胞瘤是最常见的儿童PNETs。髓母细胞瘤和其他PNET中的肿瘤细胞类似于发育中的中枢神经系统的前体细胞，但它们也可能表现出未成熟神经元或神经胶质的分子表型。由于神经营养因子在正常发育的中枢神经系统中调节分化、增殖和细胞死亡，并且最近的证据表明神经营养因子可能影响髓母细胞瘤的行为，我们研究了29例PNET活检样本(其中27例是后颅窝髓母细胞瘤)，采用针对每个主要高亲和力神经营养素受体蛋白TrkA和TrkC的抗体进行免疫组化研究。TrkA、TrkB和TrkC分别在20%、50%的PNETs肿瘤细胞中呈阳性表达。TrkA和TrkB主要在滤泡结构中表达，TrkC在未分化的肿瘤细胞中表达，在滤泡结构中不表达。使用主要激活TrkB和TrkC的神经营养因子抗体对这些PNETs中的一个亚群，即脑源性神经营养因子、神经营养因子-3和神经营养因子-4/5进行的免疫组织化学研究表明，免疫活性的脑源性神经营养因子、神经营养因子-3和神经营养因子-4/5分别在20%、10%和20%的PNET活检组织中检测到。