Expression of Hedgehog ligand and signal transduction components in mutually distinct isocitrate dehydrogenase mutant glioma cells supports a role for paracrine signaling

在不同的异柠檬酸脱氢酶突变型胶质瘤细胞中,Hedgehog配体和信号转导成分的表达支持旁分泌信号的作用。

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Abstract

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.

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