Inflammatory cytokine modulation of matrix metalloproteinase expression and invasiveness of glioma cells in a 3-dimensional collagen matrix.
Glioma invasiveness is accomplished in part by matrix metalloproteinases (MMPs) which remodel the constraints of the three dimensional (3D) matrix of the brain parenchyma. Tissue culture studies have advanced knowledge of glioma invasiveness but the majority of studies have used a two dimensional (2D) monolayer culture system which does not reproduce the spatial constraints of invasiveness in vivo. Here, we have used a 3D matrix of type I collagen (CL) gel to address glioma invasiveness in vitro. We show that in 3D CL matrix, interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), cytokines which are elevated in gliomas in vivo, increased glioma cell invasiveness with correspondent elevation of MMP-2 and MMP-9. Cytokine-stimulated glioma invasiveness was blocked by three pharmacological metalloproteinase inhibitors and by small interfering RNAs to MMP-2. Thus, in 3D matrix of CL, MMP-2 expression is modulated by inflammatory cytokines with the concomitant increase in glioma invasiveness.
Sarkar
Susobhan
S
Department of Oncology, University of Calgary, Calgary, AB, Canada.
Yong
V Wee
VW
D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003094:Collagen; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods
D000970:Antineoplastic Agents; D016207:Cytokines; D034741:RNA, Small Interfering; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9