Interleukin-1-induced changes in the glioblastoma secretome suggest its role in tumor progression

Leonid Tarassishin, Jihyeon Lim, D. Brent Weatherly, Ruth H. Angeletti, Sunhee C. Lee

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The tumor microenvironment including glial cells and their inflammatory products regulates brain tumor development and progression. We have previously established that human glioma cells are exquisitely sensitive to IL-1 stimulation leading us to undertake a comparative analysis of the secretome of unstimulated and cytokine (IL-1)-stimulated glioblastoma cells. We performed label-free quantitative proteomic analysis and detected 190 proteins which included cytokines, chemokines, growth factors, proteases, cell adhesion molecules, extracellular matrix (ECM) and related proteins. Measuring area under the curve (AUC) of peptides for quantitation, the IL-1-induced secretome contained 13 upregulated and 5 downregulated extracellular proteins (p. <. 0.05) compared to controls. Of these, IL-8, CCL2, TNC, Gal-1 and PTX3 were validated as upregulated and SERPINE1, STC2, CTGF and COL4A2 were validated as downregulated factors by immunochemical methods. A major representation of the ECM and related proteins in the glioblastoma secretome and their modulation by IL-1 suggested that IL-1 induces its effect in part by altering TGFβ expression, activity and signaling. These findings enhance our understanding of IL-1-induced modulation of glioma microenvironment, with implications for increased tumor invasion, migration and angiogenesis. They further provide novel targets for the glioblastoma intervention.

Original languageEnglish (US)
Pages (from-to)152-168
Number of pages17
JournalJournal of Proteomics
Volume99
DOIs
StatePublished - Mar 17 2014

Keywords

  • Extracellular matrix
  • Innate immunity
  • Interleukin-1
  • Label free quantitation
  • Secretome
  • TGFβ

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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