title: Necrotic cells influence migration and invasion of glioblastoma via NF-κB/AP-1-mediated IL-8 regulation.
abstract: Glioblastoma multiforme (GBM) is the most common primary intracranial tumor in adults and has poor prognosis. Diffuse infiltration into normal brain parenchyma, rapid growth, and the presence of necrosis are remarkable hallmarks of GBM. However, the effect of necrotic cells on GBM growth and metastasis is poorly understood at present. In this study, we examined the biological significance of necrotic tissues by exploring the molecular mechanisms underlying the signaling network between necrotic tissues and GBM cells. The migration and invasion of the GBM cell line CRT-MG was significantly enhanced by treatment with necrotic cells, as shown by assays for scratch wound healing and spheroid invasion. Incubation with necrotic cells induced IL-8 secretion in CRT-MG cells in a dose-dependent manner. In human GBM tissues, IL-8 positive cells were mainly distributed in the perinecrotic region, as seen in immunohistochemistry and immunofluorescence analysis. Necrotic cells induced NF-κB and AP-1 activation and their binding to the IL-8 promoter, leading to enhanced IL-8 production and secretion in GBM cells. Our data demonstrate that when GBM cells are exposed to and stimulated by necrotic cells, the migration and invasion of GBM cells are enhanced and facilitated via NF-κB/AP-1 mediated IL-8 upregulation.
authors.affiliation: Department of Physiology, Ewha Womans University School of Medicine, Seoul 911-1, Korea.|Tissue Injury Defense Research Center , School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Department of Physiology, Ewha Womans University School of Medicine, Seoul 911-1, Korea.|Tissue Injury Defense Research Center , School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Park
authors.affiliation: Tissue Injury Defense Research Center , School of Medicine, Ewha Womans University, Seoul, Korea.|Department of Molecular Medicine , School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Ahn
authors.affiliation: Department of Pathology, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Sewha
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Pathology, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Cho
authors.affiliation: Department of Physiology, Ewha Womans University School of Medicine, Seoul 911-1, Korea.|Tissue Injury Defense Research Center , School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Jihee Lee
authors.initials: JL
authors.lastname: Kang
authors.affiliation: Department of Physiology, Ewha Womans University School of Medicine, Seoul 911-1, Korea.|Tissue Injury Defense Research Center , School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Choi
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement; D005786:Gene Expression Regulation; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009336:Necrosis; D009361:Neoplasm Invasiveness; D060066:Protein Interaction Maps; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1