Impact of IL17B on Endothelial Cells and Angiogenesis.

Abstract

Abstract Introduction:Tumour angiogenesis plays a vital role in cancer development and spread. In the current study, IL17B was found to be unregulated in endothelial cells in response to Hepatocyte Growth Factor (HGF). IL17B shares structural similarities to IL17A, which has been previously proposed to promote angiogenesis and tumourgenicity, though currently the role of this cytokine in cancer or angiogenesis is largely unknown.Methods:HECV gene expression in response to HGF treatment was examined over a wide range of genes using micro array analysis to detect differential gene expression over the U133+2 chip. Recombinant human IL17B (rhIL17B) was subsequently used to treat human HECV endothelial cells over a range of concentrations. The impact of rhIL17B on HECV cell motility and angiogenic potential was assessed using Matrigel migration/wounding and tubule formation.Results:Micro array analysis detected a significant increase in IL17B expression in response to 4 hour treatment of HECV human endothelial cells with 40ng/ml HGF (p < 0.05 vs HGF untreated HECV cells). rhIL17B negatively influenced HECV tubule formation at the higher concentrations with substantial reduction in tubule formation being seen following treatment with 250ng/ml rhIL17B. Higher concentrations of rhIL17B were also seen to reduce the capacity of HECV cells to migrate in a scratch wounding assay and significant differences in migrated distance were observed following 75 minute incubation (P < 0.05 vs control untreatment group).Conclusions:Micro array analysis suggests that IL17B gene expression in the HECV human endothelial cell line can be upregulated in response to treatment with HGF. Subsequently high levels of rhIL17B were seen to negatively impact on the tubule formation and migratory capacity of this cell line. Together this data suggests that IL17B is unlikely to play a key role in the pro-angiogenic response initiated through HGF signalling but at higher concentrations may itself be able to negatively impact the angiogenic potential of the HECV endothelial cell line. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2157.