Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype.
Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype.
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DOI：
10.1016/j.ccell.2016.03.002
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发表时间：
2016-04-11
期刊：
影响因子：
50.3
通讯作者：
Gilbertson RJ
中科院分区：
文献类型：
--
作者：
Phoenix TN;Patmore DM;Boop S;Boulos N;Jacus MO;Patel YT;Roussel MF;Finkelstein D;Goumnerova L;Perreault S;Wadhwa E;Cho YJ;Stewart CF;Gilbertson RJ
儿童脑肿瘤髓母细胞瘤包括四个亚型，具有非常不同的肿瘤。在这里，我们表明，旁分泌信号驱动的突变β-连环蛋白在WNT-髓母细胞瘤-一种基本上可治愈的形式的疾病-诱导一个异常的有孔的血管系统，允许积累高水平的肿瘤内化疗和强大的治疗反应。相比之下，SHH-成神经管细胞瘤-一种较难治愈的疾病亚型-包含完整的血脑屏障，使这种肿瘤不可渗透并对化疗具有抗性。髓母细胞瘤-内皮细胞旁分泌轴可以在体内操纵，改变化疗渗透性和临床反应。因此，髓母细胞瘤基因型决定了肿瘤血管表型，部分解释了髓母细胞瘤亚型之间的差异，并提出了一种增强其他脑肿瘤化疗反应性的方法。
The childhood brain tumour medulloblastoma includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant Beta-Catenin in WNT-medulloblastoma – an essentially curable form of the disease – induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoural chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma – a less curable disease subtype – contains an intact blood brain barrier, rendering this tumour impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumour vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumours.