Upregulation of tumour endothelial marker-8 by interleukin-1beta and its impact in IL-1beta induced angiogenesis.

Tumour endothelial marker-8 (TEM-8) has been found to be selectively upregulated in tumour-associated endothelial cells and is implicated in tumour specific angiogenesis. Specific factors, indigenous to tissues and tumours that regulate the TEM-8 mechanism in angiogenesis are not defined. We report for the first time that interleukin-1beta induces the expression of TEM-8 in endothelial cells. Human vascular endothelial cells (HECV), which strongly express IL-1beta receptor (as revealed by RT-PCR, Western blotting), increased the level of TEM-8 expression following stimulation with IL-1beta (as revealed by conventional and quantitative RT-PCR). Using a newly developed antibody to human TEM-8, we have further demonstrated that IL-1beta significantly raised the level of TEM-8 at the protein level, as revealed by Western blotting. In vitro tubule forming assay, revealed that IL-1beta significantly induced the formation of capillary-like tubules from the HECV cells, accompanied by an increase in TEM-8 expression. It is concluded that IL-1beta is a powerful regulator of the expression of TEM-8 in vascular endothelial cells. Our results suggest an important pathway through which IL-1beta regulates tumour-associated angiogenesis.