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

68 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

Fingerprint

Brevican
Cartilage Oligomeric Matrix Protein
Disintegrins
Metalloproteases
Glioblastoma
Glioma
Thrombospondin 1
Thrombospondins
Brain
Proteoglycans

Keywords

  • ADAMTS
  • Brevican
  • Digestion
  • Glioma
  • Invasion

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Nakada, M., Miyamori, H., Kita, D., Takahashi, T., Yamashita, J., Sato, H., ... 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

Human glioblastomas overexpress ADAMTS-5 that degrades brevican. / Nakada, Mitsutoshi; Miyamori, Hisashi; Kita, Daisuke; Takahashi, Tomoya; Yamashita, Junkoh; Sato, Hiroshi; Miura, Ryu; Yamaguchi, Yu; Okada, Yasunori.

In: Acta Neuropathologica, Vol. 110, No. 3, 09.2005, p. 239-246.

Research output: Contribution to journalArticle

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, vol. 110, no. 3, pp. 239-246. https://doi.org/10.1007/s00401-005-1032-6
Nakada M, Miyamori H, Kita D, Takahashi T, Yamashita J, Sato H et al. Human glioblastomas overexpress ADAMTS-5 that degrades brevican. Acta Neuropathologica. 2005 Sep;110(3):239-246. https://doi.org/10.1007/s00401-005-1032-6
Nakada, Mitsutoshi ; Miyamori, Hisashi ; Kita, Daisuke ; Takahashi, Tomoya ; Yamashita, Junkoh ; Sato, Hiroshi ; Miura, Ryu ; Yamaguchi, Yu ; Okada, Yasunori. / Human glioblastomas overexpress ADAMTS-5 that degrades brevican. In: Acta Neuropathologica. 2005 ; Vol. 110, No. 3. pp. 239-246.
@article{b84cf215cb284dbc9d38491412192f6d,
title = "Human glioblastomas overexpress ADAMTS-5 that degrades brevican",
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, Brevican, Digestion, Glioma, Invasion",
author = "Mitsutoshi Nakada and Hisashi Miyamori and Daisuke Kita and Tomoya Takahashi and Junkoh Yamashita and Hiroshi Sato and Ryu Miura and Yu Yamaguchi and Yasunori Okada",
year = "2005",
month = "9",
doi = "10.1007/s00401-005-1032-6",
language = "English",
volume = "110",
pages = "239--246",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Human glioblastomas overexpress ADAMTS-5 that degrades brevican

AU - Nakada, Mitsutoshi

AU - Miyamori, Hisashi

AU - Kita, Daisuke

AU - Takahashi, Tomoya

AU - Yamashita, Junkoh

AU - Sato, Hiroshi

AU - Miura, Ryu

AU - Yamaguchi, Yu

AU - Okada, Yasunori

PY - 2005/9

Y1 - 2005/9

N2 - 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.

AB - 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.

KW - ADAMTS

KW - Brevican

KW - Digestion

KW - Glioma

KW - Invasion

UR - http://www.scopus.com/inward/record.url?scp=26444551181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26444551181&partnerID=8YFLogxK

U2 - 10.1007/s00401-005-1032-6

DO - 10.1007/s00401-005-1032-6

M3 - Article

VL - 110

SP - 239

EP - 246

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

IS - 3

ER -