title: Interleukin-1-induced changes in the glioblastoma secretome suggest its role in tumor progression.
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.
  
  
  CONCLUSIONS
  Present study is on an unbiased screening of the glioblastoma secretome stimulated by IL-1 which triggers neuroinflammatory cascades in the central nervous system. Network of secreted proteins were shown to be regulated revealing their possible contribution to glioma progression. Label free quantitative proteomics has provided unique novel targets for potential glioblastoma intervention.
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx NY 10461.
authors: Leonid
authors: L
authors: Tarassishin
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx NY 10461.|Laboratory for Macromolecular Analysis & Proteomics, Albert Einstein College of Medicine, Bronx NY 10461.
authors: Jihyeon
authors: J
authors: Lim
authors: Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602.
authors: D Brent
authors: DB
authors: Weatherly
authors: Laboratory for Macromolecular Analysis & Proteomics, Albert Einstein College of Medicine, Bronx NY 10461.|Department of Developmental & Molecular Biology, Albert Einstein College of Medicine, Bronx NY 10461.
authors: Ruth H
authors: RH
authors: Angeletti
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx NY 10461.
authors: Sunhee C
authors: SC
authors: Lee
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D007375:Interleukin-1; D009363:Neoplasm Proteins; D020543:Proteome
keywords: Extracellular matrix; Innate immunity; Interleukin-1; Label free quantitation; Secretome; TGFβ