Induced interleukin-33 expression enhances the tumorigenic activity of rat glioma cells
Open Access
- 9 December 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in Neuro-Oncology
- Vol. 16 (4), 552-566
- https://doi.org/10.1093/neuonc/not234
Abstract
Glioma development is a multistep process associated with progressive genetic alterations but also regulated by cellular and noncellular components in a tumor-associated niche. Using 2 rat C6 glioma cell clones with different tumorigenesis, named C6-1 and C6-2, this study characterized genes associated with enhanced tumorigenic features of glioma cells by comparative cDNA microarray analysis combined with Q-PCR. Neurospehere formation and clonogenicity were examined to determine the growth of tumorigenic C6 glioma cells. The lentivirus-mediated gene knockdown approach was conducted to determine the role of interleukin-33 (IL-33) in glioma cell proliferation and migration. Transwell cell invasion assay was used to examine microglia migration induced by tumorigenic C6 cells. The functional analysis of gene ontology (GO) biological processes shows that the upregulated genes found in tumorigenic C6 (C6-1) cells are closely related to cell proliferation. Tumorigenic C6 cells expressed cytokines and chemokines abundantly. Among these genes, IL-33 was profoundly induced in tumorigenic C6 cells with the expression of IL-33 receptor ST2. Furthermore, the growth rate and colony formation of tumorigenic C6 cells were attenuated by the inhibition of IL-33 and ST2 gene expression. Moreover, IL-33 was involved in tumorigenic glioma cell migration and regulation of the expression of several glioma-associated growth factors and chemokines in tumorigenic C6 cells. Accordingly, we concluded that glioma cells with abundant production of IL-33 grow rapidly; moreover, the interactions of multiple cytokines/chemokines induced by glioma cells may develop a microenvironment that facilitates microglia/macrophage infiltration and fosters glioma growth in the brain.Keywords
This publication has 51 references indexed in Scilit:
- Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF‐A and TGFβ2 in vascular abnormalizationThe Journal of Pathology, 2012
- Production and functions of IL-33 in the central nervous systemBrain Research, 2011
- Role of IL-33 in inflammation and diseaseJournal of Inflammation, 2011
- Gene expression profiling of gliomas: merging genomic and histopathological classification for personalised therapyBritish Journal of Cancer, 2010
- Therapeutic Targets in Malignant Glioblastoma MicroenvironmentSeminars in Radiation Oncology, 2009
- Hypoxia enhances CXCR4 expression favoring microglia migration via HIF-1α activationBiochemical and Biophysical Research Communications, 2008
- Glioma Stem Cells: A Midterm ExamNeuron, 2008
- Tetramethylpyrazine inhibits activities of glioma cells and glutamate neuro-excitotoxicity: Potential therapeutic application for treatment of gliomasNeuro-Oncology, 2008
- CXCR4 engagement promotes dendritic cell survival and maturationBiochemical and Biophysical Research Communications, 2007
- Antiangiogenics: The Potential Role of Integrating This Novel Treatment Modality With Chemoradiation for Solid CancersJournal of Clinical Oncology, 2007