Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells.
The hedgehog (Hh) signaling pathway regulates progenitor cells during embryogenesis and tumorigenesis in multiple organ systems. We have investigated the activity of this pathway in adult gliomas, and demonstrate that the Hh pathway is operational and activated within grade II and III gliomas, but not grade IV de novo glioblastoma multiforme. Furthermore, our studies reveal that pathway activity and responsiveness is confined to progenitor cells within these tumors. Additionally, we demonstrate that Hh signaling in glioma progenitor cells is ligand-dependent and provide evidence documenting the in vivo source of Sonic hedgehog protein. These findings suggest a regulatory role for the Hh pathway in progenitor cells within grade II and III gliomas, and the potential clinical utility of monitoring and targeting this pathway in these primary brain tumors.
Ehtesham
M
M
Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN 37232, USA.
Sarangi
A
A
Valadez
J G
JG
Chanthaphaychith
S
S
Becher
M W
MW
Abel
T W
TW
Thompson
R C
RC
Cooper
M K
MK
D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000145:classification / Q000235:genetics*; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D008024:Ligands; D051379:Mice; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000502:physiology*; D000072079:Patched Receptors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D014407:Tumor Cells, Cultured; D000071676:Zinc Finger Protein GLI1
C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D008024:Ligands; D000072079:Patched Receptors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1