Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells
Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells
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DOI：
10.1038/sj.onc.1210359
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发表时间：
2007-08-01
期刊：
影响因子：
8
通讯作者：
Cooper, M. K.
中科院分区：
文献类型：
--
作者：
Ehtesham, M.;Sarangi, A.;Cooper, M. K.
Hedgehog(HH)信号通路在多器官系统的胚胎发生和肿瘤发生过程中调节祖细胞。我们已经研究了这一通路在成人胶质瘤中的活性，并证明HH通路在II级和III级胶质瘤中是可操作和激活的，但在IV级多形性胶质母细胞瘤中不是。此外，我们的研究表明，通路的活性和反应性仅限于这些肿瘤中的祖细胞。此外，我们证明了神经胶质瘤前体细胞中的HH信号是配体依赖的，并为证明Sonic Hedgehog蛋白的体内来源提供了证据。这些发现提示HH通路在II级和III级胶质瘤中的前体细胞中的调节作用，以及在这些原发脑瘤中监测和靶向这一通路的潜在临床实用价值。
The hedgehog (Hh) signaling pathway regulates progenitor cells during embryogenesis and tumorigenesis in multiple organ systems. We have investigated the activity of this pathway in adult gliomas, and demonstrate that the Hh pathway is operational and activated within grade II and III gliomas, but not grade IV de novo glioblastoma multiforme. Furthermore, our studies reveal that pathway activity and responsiveness is confined to progenitor cells within these tumors. Additionally, we demonstrate that Hh signaling in glioma progenitor cells is ligand-dependent and provide evidence documenting the in vivo source of Sonic hedgehog protein. These findings suggest a regulatory role for the Hh pathway in progenitor cells within grade II and III gliomas, and the potential clinical utility of monitoring and targeting this pathway in these primary brain tumors.