TY - JOUR
T1 - Interleukin-1-induced changes in the glioblastoma secretome suggest its role in tumor progression
AU - Tarassishin, Leonid
AU - Lim, Jihyeon
AU - Weatherly, D. Brent
AU - Angeletti, Ruth H.
AU - Lee, Sunhee C.
N1 - Funding Information:
This study was supported by NIH RO1 MH55477 , Einstein CFAR , NCRR 1S10RR021056 , and NCRR 1S10RR15859 . The authors are grateful to Dr. Yungtai Lo for many helpful discussions.
PY - 2014/3/17
Y1 - 2014/3/17
N2 - 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.
AB - 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.
KW - Extracellular matrix
KW - Innate immunity
KW - Interleukin-1
KW - Label free quantitation
KW - Secretome
KW - TGFβ
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U2 - 10.1016/j.jprot.2014.01.024
DO - 10.1016/j.jprot.2014.01.024
M3 - Article
C2 - 24503185
AN - SCOPUS:84894288399
SN - 1874-3919
VL - 99
SP - 152
EP - 168
JO - Journal of Proteomics
JF - Journal of Proteomics
ER -