title: Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma.
abstract: BACKGROUND
  Meningiomas are the most common type of intracranial tumor, accounting for between 24 and 30 % of primary intracranial tumors. Thus far, no biomarkers exist to reliably predict the clinical outcome of meningiomas. A previous genome-wide methylation analysis revealed that HOXA9 is one of the most functionally relevant biomarkers. In this study, we have examined whether HOXA9 is a potential therapeutic target in meningiomas, using HXR9, a peptide inhibitor of the interaction between HOXA9 and its cofactor PBX.
  
  
  METHODS
  We determined the expression level of HOXA9 in human meningiomas, meningioma cell lines, and normal brain tissue. Meningioma in culture and in subcutaneous tumors was treated with HXR9. We also examined the disruption of HOXA9/PBX dimers.
  
  
  RESULTS
  We first confirmed that HOXA9 is highly expressed in meningiomas, but not in normal brain tissue. The HXR9 peptide blocks the binding of HOXA9 to PBX, leading to an alteration of DNA binding, and subsequent regulation of their target genes. HXR9 markedly inhibited the growth of meningioma cells and subcutaneous meningeal tumors.
  
  
  CONCLUSIONS
  There is no effective chemotherapy for meningiomas at present, and targeting the HOXA9/PBX interaction may represent a novel treatment option for this disease.
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Nagoya University, 65, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.forename: Atsushi
authors.initials: A
authors.lastname: Natsume
authors.forename: Takeshi
authors.initials: T
authors.lastname: Senga
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ito
authors.forename: Masasuke
authors.initials: M
authors.lastname: Ohno
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Iwami
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Ohka
authors.forename: Kazuya
authors.initials: K
authors.lastname: Motomura
authors.forename: Sayano
authors.initials: S
authors.lastname: Kinjo
authors.forename: Maki
authors.initials: M
authors.lastname: Ito
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Richard
authors.initials: R
authors.lastname: Morgan
authors.forename: Toshishiko
authors.initials: T
authors.lastname: Wakabayashi
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008579:Meningioma / Q000188:drug therapy* / Q000473:pathology; D008969:Molecular Sequence Data; D010455:Peptides / Q000627:therapeutic use*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C522972:HXR9 peptide; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014157:Transcription Factors; C097899:homeobox protein HOXA9