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.

• Authors: Mitsutoshi Nakada, Hisashi Miyamori, Daisuke Kita, Tomoya Takahashi, Junkoh Yamashita, Hiroshi Sato, Ryu Miura, Yu Yamaguchi, Yasunori Okada
• Journal: Acta neuropathologica (Acta Neuropathol) Vol. 110 Issue 3 Pg. 239-46 (Sep 2005) ISSN: 0001-6322 [Print] Germany
• PMID: 16133547 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• BCAN protein, human
• Biomarkers, Tumor
• Brevican
• Chondroitin Sulfate Proteoglycans
• Lectins, C-Type
• Nerve Tissue Proteins
• RNA, Messenger
• ADAM Proteins
• ADAMTS1 Protein
• ADAMTS1 protein, human
• ADAMTS5 Protein
• ADAMTS5 protein, human
• Procollagen N-Endopeptidase
• ADAMTS4 Protein
• ADAMTS4 protein, human

Topics

• ADAM Proteins (analysis, genetics, metabolism)
• ADAMTS1 Protein
• ADAMTS4 Protein
• ADAMTS5 Protein
• Adult
• Aged
• Biomarkers, Tumor (analysis, metabolism)
• Brain Neoplasms (diagnosis, metabolism, physiopathology)
• Brevican
• Cell Line, Tumor
• Chondroitin Sulfate Proteoglycans (metabolism)
• Extracellular Matrix (metabolism)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Glioblastoma (diagnosis, metabolism, physiopathology)
• Humans
• Lectins, C-Type (metabolism)
• Male
• Middle Aged
• Neoplasm Invasiveness (physiopathology)
• Nerve Tissue Proteins (metabolism)
• Procollagen N-Endopeptidase (genetics, metabolism)
• RNA, Messenger (analysis, metabolism)
• Transfection
• Up-Regulation (genetics)