Expression of Hedgehog ligand and signal transduction components in mutually distinct isocitrate dehydrogenase mutant glioma cells supports a role for paracrine signaling.
Expression of Hedgehog ligand and signal transduction components in mutually distinct isocitrate dehydrogenase mutant glioma cells supports a role for paracrine signaling.
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Hedgehog 配体和信号转导成分在相互不同的异柠檬酸脱氢酶突变神经胶质瘤细胞中的表达支持旁分泌信号传导的作用。
DOI：
10.1007/s11060-014-1481-7
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发表时间：
2014
影响因子：
3.9
通讯作者：
Cooper,MichaelK
中科院分区：
文献类型：
--
作者：
Abiria,SundayA;Williams,ThomasV;Munden,AlexanderL;Grover,VandanaK;Wallace,Ato;Lundberg,ChristopherJ;Valadez,JGerardo;Cooper,MichaelK
Hedgehog（Hh）信号通过配体依赖性机制调节恶性胶质瘤的生长。由于缺乏明确鉴定胶质瘤标本中肿瘤细胞的方法，Sonic Hh配体的细胞来源和信号传导模式尚未明确定义。使用突变型异柠檬酸脱氢酶蛋白表达的特异性抗体来鉴定神经胶质瘤细胞，我们证明了Sonic Hh配体和途径组分Patched 1（PTCH 1）和GLI 1在肿瘤细胞中表达。此外，Sonic Hh配体及其转录靶标PTCH 1和GLI 1在肿瘤细胞的相互不同的群体中表达。这些发现支持恶性胶质瘤瘤内Hh信号的旁分泌模式。
Hedgehog (Hh) signaling regulates the growth of malignant gliomas by a ligand-dependent mechanism. The cellular source of Sonic Hh ligand and mode of signaling have not been clearly defined due to the lack of methods to definitively identify neoplastic cells in glioma specimens. Using an antibody specific for mutant isocitrate dehydrogenase protein expression to identify glioma cells, we demonstrate that Sonic Hh ligand and the pathway components Patched1 (PTCH1) and GLI1 are expressed in neoplastic cells. Further, Sonic Hh ligand and its transcriptional targets, PTCH1 and GLI1, are expressed in mutually distinct populations of neoplastic cells. These findings support a paracrine mode of intratumoral Hh signaling in malignant gliomas.