A perivascular niche for brain tumor stem cells
A perivascular niche for brain tumor stem cells
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DOI：
10.1016/j.ccr.2006.11.020
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发表时间：
2007-01-01
期刊：
影响因子：
50.3
通讯作者：
Gilbertson, Richard J.
中科院分区：
文献类型：
--
作者：
Calabrese, Christopher;Poppleton, Helen;Gilbertson, Richard J.
癌症被认为来自癌症干细胞(CSCs)，但目前尚不清楚这些细胞是否仍然依赖于调节正常干细胞的利基微环境。我们发现，内皮细胞与自我更新的脑肿瘤细胞密切相互作用，并分泌维持这些细胞处于干细胞样状态的因子。增加原位脑瘤移植瘤内皮细胞或血管的数量，可扩大肿瘤细胞的自我更新比例，加速肿瘤的发生和生长。相反，耗尽异种移植物的血管会消融肿瘤的自我更新细胞，阻止肿瘤的生长。我们认为大脑CSCs维持在血管内，这是治疗方法的重要靶点。
Cancers are believed to arise from cancer stem cells (CSCs), but it is not known if these cells remain dependent upon the niche microenvironments that regulate normal stem cells. We show that endothelial cells interact closely with self-renewing brain tumor cells and secrete factors that maintain these cells in a stem cell-like state. Increasing the number of endothelial cells or blood vessels in orthotopic brain tumor xenografts expanded the fraction of self-renewing cells and accelerated the initiation and growth of tumors. Conversely, depletion of blood vessels from xenografts ablated self-renewing cells from tumors and arrested tumor growth. We propose that brain CSCs are maintained within vascular niches that are important targets for therapeutic approaches.