期刊
CANCER CELL
卷 29, 期 4, 页码 508-522出版社
CELL PRESS
DOI: 10.1016/j.ccell.2016.03.002
关键词
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资金
- NIH [P01CA96832, P30CA021765]
- American Lebanese Syrian Associated Charities
- Cancer Research UK
- Cancer Research UK [22492] Funding Source: researchfish
The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we showthat 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-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor 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 tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors.
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