Necrotic cells influence migration and invasion of glioblastoma via NF-γ° B/AP-1-mediated IL-8 regulation

So Hee Ahn, Hyunju Park, Young Ho Ahn, Sewha Kim, Min Sun Cho, Jihee Lee Kang, Youn Hee Choi

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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-κ B 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-κ B/AP-1 mediated IL-8 upregulation.

Original languageEnglish
Article number24552
JournalScientific Reports
StatePublished - 14 Apr 2016

Bibliographical note

Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) Grant 2012R1A5A2A32671866 and by NRF-2013R1A1A3 009978.


Dive into the research topics of 'Necrotic cells influence migration and invasion of glioblastoma via NF-γ° B/AP-1-mediated IL-8 regulation'. Together they form a unique fingerprint.

Cite this