SPARC upregulates MT1-MMP expression, MMP-2 activation, and the secretion and cleavage of galectin-3 in U87MG glioma cells

NEUROSCIENCE LETTERS

卷:419

Article

McClung, Heather M. ; Thomas, Stacey L. ; Osenkowski, Pamela ; Toth, Marta ; Menon, Priya ; Raze, Avraham ; Fridman, Rafael ; Rempel, Sandra A.

关键词: SPARC;    MMP-2;    MT1-MMP;    galectin-3;    glioma;    invasion;   

DOI  :  10.1016/j.neulet.2007.04.037

来源: Elsevier

【 摘 要 】

Secreted protein acidic and rich in cysteine (SPARC) is highly expressed in human gliomas and promotes glioma invasion. We have shown by cDNA array analysis that SPARC upregulates membrane type 1-matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) transcripts. To confirm these findings at the protein level and determine whether SPARC expression correlates with increased MMP activity, we used Western blot to assess the levels of MT1-MMP, and gelatin zymography to assess MMP-2 levels and activity. We also examined the expression, secretion, and cleavage of galectin-3, a target of MT1-MMP and MMP-2. Our data confirm that SPARC upregulates MT1-MMP levels and MMP-2 activity. There was also an increase in secreted galectin-3, as well as an increase in the proteolytically processed form of galectin-3. Previous studies have demonstrated that MT1-MMP MMP-2, and galectin-3 are increased in gliomas. Our results suggest that their upregulation and activation may be a consequence of increased SPARC expression. These data provide a provisional mechanism whereby SPARC contributes to brain tumor invasion. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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