Ehtesham M, Sarangi A, Valadez J G, Chanthaphaychith S, Becher M W, Abel T W, Thompson R C, Cooper M K
Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN 37232, USA.
Oncogene. 2007 Aug 23;26(39):5752-61. doi: 10.1038/sj.onc.1210359. Epub 2007 Mar 12.
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.
刺猬（Hh）信号通路在胚胎发育和多个器官系统的肿瘤发生过程中调节祖细胞。我们研究了该通路在成人胶质瘤中的活性，结果表明Hh通路在II级和III级胶质瘤中起作用并被激活，但在IV级原发性多形性胶质母细胞瘤中则不然。此外，我们的研究表明，该通路的活性和反应性局限于这些肿瘤内的祖细胞。另外，我们证明胶质瘤祖细胞中的Hh信号传导是配体依赖性的，并提供了记录音猬因子蛋白体内来源的证据。这些发现提示Hh通路在II级和III级胶质瘤的祖细胞中具有调节作用，以及在这些原发性脑肿瘤中监测和靶向该通路的潜在临床应用价值。
