Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas Journal Article
| Authors: | Becher, O. J.; Hambardzumyan, D.; Fomchenko, E. I.; Momota, H.; Mainwaring, L.; Bleau, A. M.; Katz, A. M.; Edgar, M.; Kenney, A. M.; Cordon-Cardo, C.; Blasberg, R. G.; Holland, E. C. |
| Article Title: | Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas |
| Abstract: | 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 β-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. ©2008 American Association for Cancer Research. |
| Keywords: | platelet derived growth factor; controlled study; protein expression; unclassified drug; nonhuman; glioma; brain neoplasms; cancer grading; protein function; protein localization; cell proliferation; animal cell; mouse; animals; mice; animal tissue; oligodendrocyte transcription factor 2; sonic hedgehog protein; animal experiment; animal model; astrocyte; hedgehog proteins; down-regulation; enzyme activity; cell line, tumor; carcinogenesis; mice, transgenic; transcription factors; endothelium cell; glioblastoma; newborn; platelet-derived growth factor; tumor cell; kruppel-like transcription factors; beta galactosidase; oligodendroglioma; down regulation; genes, reporter; microenvironment; stroma cell; brain region; bioluminescence; astrocytes; beta-galactosidase; nucleic acid binding protein; protein gli |
| Journal Title: | Cancer Research |
| Volume: | 68 |
| Issue: | 7 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2008-04-01 |
| Start Page: | 2241 |
| End Page: | 2249 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-07-6350 |
| PUBMED: | 18381430 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 43" - "Export Date: 17 November 2011" - "CODEN: CNREA" - "Source: Scopus" |
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