title: Expression of Hedgehog ligand and signal transduction components in mutually distinct isocitrate dehydrogenase mutant glioma cells supports a role for paracrine signaling.
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.
authors.affiliation: Department of Neurology, Vanderbilt University Medical Center, MRB III, Rm. 6160, 465 21st Avenue South, Nashville, TN, 37232, USA.
authors.forename: Sunday A
authors.initials: SA
authors.lastname: Abiria
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Williams
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Munden
authors.forename: Vandana K
authors.initials: VK
authors.lastname: Grover
authors.forename: Ato
authors.initials: A
authors.lastname: Wallace
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lundberg
authors.forename: J Gerardo
authors.initials: JG
authors.lastname: Valadez
authors.forename: Michael K
authors.initials: MK
authors.lastname: Cooper
mesh_terms: D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019899:Paracrine Communication / Q000502:physiology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human