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

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• 作者：Heather M. McClung ; Stacey L. Thomas ; Pamela Osenkowski ; Marta Toth ; Priya Menon ; Avraham Raz ; Rafael Fridman ; S ; ra A. Rempel
• 关键词：SPARC ; MMP-2 ; MT1-MMP ; Galectin-3 ; Glioma ; Invasion
• 刊名：Neuroscience Letters
• 出版年：2007
• 出版时间：29 May 2007
• 年：2007
• 卷：419
• 期：2
• 页码：172-177
• 全文大小：470 K

文摘

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.