Oncotarget

Research Papers:

IL-8 associates with a pro-angiogenic and mesenchymal subtype in glioblastoma

Siobhan Conroy, Frank A.E. Kruyt, Michiel Wagemakers, Krishna P.L. Bhat and Wilfred F.A. den Dunnen _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:15721-15731. https://doi.org/10.18632/oncotarget.24595

Metrics: PDF 795 views  |   HTML 1212 views  |   ?  


Abstract

Siobhan Conroy1,2, Frank A.E. Kruyt3, Michiel Wagemakers4, Krishna P.L. Bhat2,* and Wilfred F.A. den Dunnen1,*

1Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

2Department of Translational Molecular Pathology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA

3Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

4Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

*These authors share senior authorship

Correspondence to:

Wilfred F.A. den Dunnen, email: w.f.a.den.dunnen@umcg.nl

Keywords: glioblastoma; subclasses; angiogenesis; IL-8

Received: September 07, 2017     Accepted: February 10, 2018     Epub: February 28, 2018     Published: March 20, 2018

ABSTRACT

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by a high rate of vascularization. However, therapeutic targeting of the vasculature through anti-vascular endothelial growth factor (VEGF) treatment has been disappointing, for which Angiopoietin-2 (Ang-2) upregulation has partly been held accountable. In this study we therefore explored the interplay of Ang-2 and VEGFA and their effect on angiogenesis in GBM, especially in the context of molecular subclasses. In a large patient cohort we identified that especially combined high expression of Ang-2 and VEGFA predicted poor overall survival of GBM patients. The high expression of both factors was also associated with increased IL-8 expression in GBM tissues, but in vitro stimulation with Ang-2 and/or VEGFA did not indicate tumor or endothelial cell-specific IL-8 responses. Glioblastoma stem cells (GSCs) of the mesenchymal (MES) subtype showed dramatically higher expression of IL8 when compared to proneural (PN) GSCs. Secreted IL-8 derived from MES GSCs induced endothelial proliferation and tube formation, and the MES GBMs had increased counts of proliferating endothelial cells. Our results highlight a critical pro-angiogenic role of IL-8 in MES GBMs.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 24595