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

Research output: Contribution to journalArticle

71 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)239-246
Number of pages8
JournalActa Neuropathologica
Volume110
Issue number3
DOIs
Publication statusPublished - 2005 Sep 1

Keywords

  • ADAMTS
  • Brevican
  • Digestion
  • Glioma
  • Invasion

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Nakada, M., Miyamori, H., Kita, D., Takahashi, T., Yamashita, J., Sato, H., Miura, R., Yamaguchi, Y., & Okada, Y. (2005). Human glioblastomas overexpress ADAMTS-5 that degrades brevican. Acta Neuropathologica, 110(3), 239-246. https://doi.org/10.1007/s00401-005-1032-6