HSP27 mediates SPARC-induced changes in glioma morphology, migration, and invasion

William A. Golembieski, Stacey L. Thomas, Chad R. Schultz, Christopher K. Yunker, Heather M. McClung, Nancy Lemke, Simona Cazacu, Thomas Barker, E. Helene Sage, Chaya Brodie, Sandra A. Rempel

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Secreted protein acidic and rich in cysteine (SPARC) regulates cell-extracellular matrix interactions that influence cell adhesion and migration. We have demonstrated that SPARC is highly expressed in human gliomas, and it promotes brain tumor invasion in vitro and in vivo. To further our understanding regarding SPARC function in glioma migration, we transfected SPARC-green fluorescent protein (GFP) and control GFP vectors into U87MG cells, and assessed the effects of SPARC on cell morphology, migration, and invasion after 24 h. The expression of SPARC was associated with elongated cell morphology, and increased migration and invasion. The effects of SPARC on downstream signaling were assessed from 0 to 6 h and 24 h. SPARC increased the levels of total and phosphorylated HSP27; the latter was preceded by activation of p38 MAPK and inhibited by the p38 MAPK inhibitor SB203580. Augmented expression of SPARC was correlated with increased levels of HSP27 mRNA. In a panel of glioma cell lines, increasing levels of SPARC correlated with increasing total and phosphorylated HSP27. SPARC and HSP27 were colocalized to invading cells in vivo. Inhibition of HSP27 mRNA reversed the SPARC-induced changes in cell morphology, migration, and invasion in vitro. These data indicate that HSP27, a protein that regulates actin polymerization cell contraction, and migration, is a novel downstream effector of SPARC-regulated cell morphology and migration. As such, it is a potential therapeutic target to inhibit SPARC-induced glioma invasion.

Original languageEnglish
Pages (from-to)1061-1075
Number of pages15
JournalGLIA
Volume56
Issue number10
DOIs
StatePublished - 1 Aug 2008
Externally publishedYes

Keywords

  • Brain tumors
  • Cell morphology
  • Cell movement
  • Intracellular signaling
  • Matricellular protein
  • Stress response protein

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