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Publication : Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas.

First Author  Becher OJ Year  2008
Journal  Cancer Res Volume  68
Issue  7 Pages  2241-9
PubMed ID  18381430 Mgi Jnum  J:133329
Mgi Id  MGI:3778267 Doi  10.1158/0008-5472.CAN-07-6350
Citation  Becher OJ, et al. (2008) Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas. Cancer Res 68(7):2241-9
abstractText  Gli signaling is critical for central nervous system development and is implicated in tumorigenesis. To monitor Gli signaling in gliomas in vivo, we created platelet-derived growth factor-induced gliomas in a Gli-luciferase reporter mouse. We find that Gli activation is found in gliomas and correlates with grade. In addition, we find that sonic hedgehog (SHH) is expressed in these tumors and also correlates with grade. We identify microvascular proliferation and pseudopalisades, elements that define high-grade gliomas as SHH-producing microenvironments. We describe two populations of SHH-producing stromal cells that reside in perivascular niche (PVN), namely low-cycling astrocytes and endothelial cells. Using the Ptc-LacZ knock-in mouse as a second Gli responsive reporter, we show beta-galactosidase activity in the PVN and in some tumors diffusely throughout the tumor. Lastly, we observe that SHH is similarly expressed in human gliomas and note that an intact tumor microenvironment or neurosphere conditions in vitro are required for Gli activity.
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