Acta Neuropathologica

, Volume 110, Issue 3, pp 239–246

Human glioblastomas overexpress ADAMTS-5 that degrades brevican

  • Mitsutoshi Nakada
  • Hisashi Miyamori
  • Daisuke Kita
  • Tomoya Takahashi
  • Junkoh Yamashita
  • Hiroshi Sato
  • Ryu Miura
  • Yu Yamaguchi
  • Yasunori Okada
Regular Paper

DOI: 10.1007/s00401-005-1032-6

Cite this article as:
Nakada, M., Miyamori, H., Kita, D. et al. Acta Neuropathol (2005) 110: 239. doi:10.1007/s00401-005-1032-6

Abstract

Selective cleavage of the Glu395-Ser396 bond of brevican, one of the major proteoglycans in adult brain tissues, is thought to be important for glioma cell invasion. Our previous biochemical study demonstrated that ADAMTS-4, a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, has such an activity. In the present study, we examined brevican-degrading activities of ADAMTS-1, -4 and -5 at the cellular level, and their expression and localization in human glioma tissues. In 293T transfectants expressing ADAMTS-4 or ADAMTS-5, brevican was cleaved into two major fragments in an identical pattern, but no such degradation was observed with ADAMTS-1 transfectants. When the expression levels of these ADAMTS species were examined by real-time quantitative PCR, only ADAMTS-5 was found to be overexpressed in glioblastoma tissues compared to control normal brain tissues (P <0.05). In situ hybridization and immunohistochemistry demonstrated that ADAMTS-5 is expressed predominantly in glioblastoma cells. Forced expression of ADAMTS-5 in glioma cell lines stimulated cell invasion. These results demonstrate for the first time that ADAMTS-5 is capable of degrading brevican and is overexpressed in glioblastoma cells, and suggest that ADAMTS-5 may play a role in glioma cell invasion through the cleavage of brevican.

Keywords

ADAMTS Glioma Invasion Brevican Digestion 

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Mitsutoshi Nakada
    • 1
    • 2
  • Hisashi Miyamori
    • 2
  • Daisuke Kita
    • 1
  • Tomoya Takahashi
    • 1
  • Junkoh Yamashita
    • 1
  • Hiroshi Sato
    • 2
  • Ryu Miura
    • 3
  • Yu Yamaguchi
    • 3
  • Yasunori Okada
    • 4
  1. 1.Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical ScienceKanazawa UniversityIshikawaJapan
  2. 2.Department of Molecular Virology and Oncology, Cancer Research InstituteKanazawa UniversityIshikawaJapan
  3. 3.The Burnham InstituteLa JollaUSA
  4. 4.Department of Pathology, School of MedicineKeio UniversityTokyoJapan

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