Induced interleukin-33 expression enhances the tumorigenic activity of rat glioma cells

Background. Glioma development is a multistep process associated with progressive genetic alterations but also regulated by cellular and noncellular components in a tumor-associated niche. Methods.Using2ratC6gliomacellcloneswithdifferenttumorigenesis,namedC6-1andC6-2,thisstudycharacterizedgenesassociated 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 approachwasconductedtodetermine theroleof interleukin-33 (IL-33) in gliomacellproliferationand migration. Transwell cell invasion assay was used to examine microglia migration induced by tumorigenic C6 cells. Results. 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-33wasprofoundlyinducedintumorigenicC6cellswiththeexpressionofIL-33receptorST2.Furthermore,thegrowthrateand 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. Conclusion. 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.