Role of IL-8 induced angiogenesis in uveal melanoma

Summary

Introduction Uveal melanoma (UM) is a highly vascularised tumour generally treated with radiotherapy (RT). A recent preclinical study from our group [1] demonstrated that RT-associated anti-angiogenic therapy has more than additive effects on cell growth, by modulating vascular endothelial growth factor (VEGF) levels. The pro-angiogenic interleukin-8 (IL-8) is highly expressed in both tumour and endothelial cells and is associated with resistance to VEGF-targeted therapies in various tumour types. The aim of this study is to investigate IL-8 release in response to the anti-angiogenic drug bevacizumab (AV) and RT given alone and in combination. Material and methods The human ocular melanoma cells (OCM-1) and human umbilical vein endothelial cells (HUVEC) were grown in transwell plates. AV was administered at a 2,500 μg/ml dose and cells were irradiated with a 6 Gy dose. IL-8 concentrations were determined by ELISA assay. Protein expression was detected by western blot. Results AV alone or in combination with RT reduces VEGF levels in both cell lines when co-cultured; unexpectedly, RT alone did not increase VEGF levels. In transwell plate AV alone lowered IL-8 secretion in both cell lines. This inhibitory effect was reduced when co-cultured cells are treated with AV + RT, suggesting that RT-induced VEGF may reactivate IL-8 secretion, enhancing an alternative pathway to sustain tumour angiogenesis. Conclusions These data indicate that the UM microenvironment, beside VEGF, can activate IL-8 signalling as an alternative pro-angiogenic pathway.