title: SPARC upregulates MT1-MMP expression, MMP-2 activation, and the secretion and cleavage of galectin-3 in U87MG glioma cells.
abstract: 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.
authors.affiliation: Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: McClung
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Thomas
authors.forename: Pamela
authors.initials: P
authors.lastname: Osenkowski
authors.forename: Marta
authors.initials: M
authors.lastname: Toth
authors.forename: Priya
authors.initials: P
authors.lastname: Menon
authors.forename: Avraham
authors.initials: A
authors.lastname: Raz
authors.forename: Rafael
authors.initials: R
authors.lastname: Fridman
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Rempel
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D015676:Osteonectin / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D037502:Galectin 3; D015676:Osteonectin; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14