title: Induced interleukin-33 expression enhances the tumorigenic activity of rat glioma cells.
abstract: 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
  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.
  
  
  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-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.
  
  
  CONCLUSIONS
  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.
authors: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan City, Taiwan (K.M.F., T.C.L., T.C.C., S.F.T.); Center for Nanomedicine Research, National Health Research Institutes, Zhunan, Taiwan (C.S.Y.).
authors: Kuan-Min
authors: KM
authors: Fang
authors: Chung-Shi
authors: CS
authors: Yang
authors: Tzu-Chien
authors: TC
authors: Lin
authors: Ti-Chun
authors: TC
authors: Chan
authors: Shun-Fen
authors: SF
authors: Tzeng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D007124:Immunoenzyme Techniques; D000067596:Interleukin-33; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D017628:Microglia / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D018925:Chemokines; D016207:Cytokines; C553108:Il33 protein, rat; D000067596:Interleukin-33; D007378:Interleukins; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: ST2; chemokine (C-C motif) ligand 7; glioma; interleukin-33; microglia