Abstract：
:Hedgehog pathway activity has been demonstrated in malignant glioma. However, its role in tumor growth has not been determined. Here we demonstrate that pharmacological inhibition of the Hedgehog pathway in established orthotopic malignant glioma xenografts confers a survival advantage. Pathway inhibition is measured in transplanted human tumor cells and not in host mouse brain. Correspondingly, survival benefit is observed only in tumors with an operational Hedgehog pathway. These data indicate that Hedgehog signaling regulates the growth of select malignant gliomas. We also demonstrate that Hedgehog pathway component and gene target expression segregate to CD133(+) tumor initiating cells. Treated mice eventually succumb to disease, thus, targeting the Hedgehog pathway in CD133(+) cells produces significant, but incomplete tumor regression. Therefore, our studies suggest that more complete tumor regression may require the inclusion of other therapeutic targets, including CD133(-) cells.
journal_name
Oncogenejournal_title
Oncogeneauthors
Sarangi A,Valadez JG,Rush S,Abel TW,Thompson RC,Cooper MKdoi
10.1038/onc.2009.208subject
Has Abstractpub_date
2009-10-01 00:00:00pages
3468-76issue
39eissn
0950-9232issn
1476-5594pii
onc2009208journal_volume
28pub_type
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