Treatment > Antiangiogenesis

Society for Neuro-Oncology Eighth Annual Meeting. Keystone, Colorado. November 13–16, 2003. Abstract No. AN-06. (Cell Culture Study)
Neuro-Oncology, Volume 5, Issue 4, October 2003

Meeting Abstract

The role of IL-8 in the regulation of normal and tumor-derived human brain endothelial cells

Christiana Charalambous^2,3, Johanna Milan⁴, Ligaya Pen², Florence Hofman², and Thomas Chen^1,2

USC Center for Brain Tumor Research, Departments of ¹Pathology, ²Neurosurgery, and ³Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA; ⁴Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, CA; USA.

Glioblastoma multiforme is characterized by vascular proliferation secondary to angiogenesis. 
Interleukin-8 (IL-8), a chemokine produced by activated endothelium and tumor cells, has been shown to induce angiogenesis. 
Since angiogenesis is critical for continued glioma growth, understanding the functional response of the endothelial cells in glioblastomas to IL-8 is essential. 
Therefore, the hypothesis of this study is that glioblastoma-derived endothelial cells (TuBEC) contribute to tumor vascularity by differential production and response to IL-8, as compared to normal brain–derived endothelial cells (BEC). 
Transwell Boyden chamber migration assays were performed to test the ability of BEC and TuBEC to migrate in response to IL-8. 
Results demonstrate that untreated TuBEC have a 50% higher migration rate than normal BEC. 
In addition, IL-8 induced BEC migration (120% increase), but had no effect on TuBEC. 
To determine whether this lack of response by the TuBEC to IL-8 was due to the endogenous production of IL-8 by these cells, we evaluated TuBEC and BEC for IL-8 production using ELISA and immunocytochemistry techniques. 
ELISA data show that TuBEC produce 2- to 3-fold higher amounts of IL-8 compared to BEC. 
Immunostaining with anti-IL-8 monoclonal antibody showed that TuBEC expressed a significantly higher percentage of positive population (80%) compared to BEC (35%). 
To further clarify whether the endogenously produced IL-8 was activating these cells in an autocrine manner, antibodies blocking the IL-8 receptors were utilized in the migration assay. 
Blocking either CXCR1 or CXCR2 partially reduced the migration of untreated TuBEC (25%), whereas antibodies to both receptors further reduced migration in an additive manner (55%). 
Antibodies to the IL-8 receptors had no effect on untreated BEC. 
These studies demonstrate that IL-8 functions in an autocrine manner in TuBEC, enabling angiogenesis to occur independently of stimulation or an outside source of growth factor. 
This is in contrast to normal BEC, where IL-8 production is highly regulated. 
Therefore, manipulation of the IL-8 response in TuBEC may represent a new target for antiangiogenic therapy.

Copyright © 2003 by the Society for Neuro-Oncology