Human glioblastomas overexpress ADAMTS-5 that degrades brevican.
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.
Nakada
Mitsutoshi
M
Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
Miyamori
Hisashi
H
Kita
Daisuke
D
Takahashi
Tomoya
T
Yamashita
Junkoh
J
Sato
Hiroshi
H
Miura
Ryu
R
Yamaguchi
Yu
Y
Okada
Yasunori
Y
D051722:ADAM Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D058581:Brevican; D045744:Cell Line, Tumor; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
C546938:BCAN protein, human; D014408:Biomarkers, Tumor; D058581:Brevican; D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human