Expression of p75NTR in fetal brain and medulloblastomas: evidence of a precursor cell marker and its persistence in neoplasia
Expression of p75NTR in fetal brain and medulloblastomas: evidence of a precursor cell marker and its persistence in neoplasia
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DOI：
10.1007/s11060-008-9755-6
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发表时间：
2009-04-01
影响因子：
3.9
通讯作者：
Tihan, Tarik
中科院分区：
文献类型：
--
作者：
Barnes, Michael;Eberhart, Charles G.;Tihan, Tarik
p75神经营养素受体（p75NTR）是肿瘤坏死因子超家族的成员，在神经系统发育中发挥重要作用。 p75NTR 在神经发生中具有双重（增殖/凋亡）作用，并以高亲和力结合前神经营养蛋白。最近的研究表明 p75NTR 在发育中的小脑和结节性/促纤维增生性髓母细胞瘤中过度表达。我们分析了胎儿和成人中枢神经系统各个部位以及 75 名髓母细胞瘤患者中的 p75NTR 表达。胎儿大脑中 p75NTR 的表达仅在外部颗粒层中可见，在浦肯野层中表达较弱，这很可能代表浦肯野细胞染色。这种染色出现在妊娠 20-40 周，而胎儿大脑的其他地方或成人小脑内没有发现染色。 p75NTR 阳性细胞的增殖标记物 ki-67 也呈阳性，但 ret、reelin、CD133、CD34 和 cleaved caspase 3 呈阴性。75 个髓母细胞瘤中有 9 个 (12%) 也显示出 p75NTR 免疫染色阳性。在四种典型、两种促纤维增生性和三种间变性髓母细胞瘤中观察到染色。 p75NTR 在一小部分髓母细胞瘤中的持续存在提出了这样的可能性：在此类肿瘤中，该受体可能是潜在的治疗靶点。
p75 neurotrophin receptor (p75NTR) is a member of the tumor necrosis factor superfamily, and plays a significant role in nervous system development. p75NTR has a dual (proliferative/apoptotic) role in neurogenesis and binds pro-neurotrophins with high affinity. Recent work suggests p75NTR is overexpressed in the developing cerebellum and in nodular/desmoplastic medulloblastomas. We analyzed p75NTR expression in various parts of the fetal and adult human central nervous system, and in 75 patients with medulloblastomas. The expression of p75NTR in the fetal brain was seen solely within the external granular layer with weaker expression in the Purkinje layer, which most likely represents Purkinje cell staining. The staining was present in gestational weeks 20-40, while no staining was identified elsewhere in the fetal brain or within the adult cerebellum. p75NTR positive cells were also positive with the proliferation marker ki-67, but were negative for ret, reelin, CD133, CD34, and cleaved caspase 3. Nine of 75 medulloblastomas (12%) were also showed positive immunostaining for p75NTR. The staining was seen in four classic, two desmoplastic, and three anaplastic medulloblastomas. The persistence of p75NTR in a small group of medulloblastomas raises the possibility that in such tumors, the receptor could be a potential therapeutic target.