Role of IL-8 induced angiogenesis in uveal melanoma
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Introduction Uveal melanoma (UM) is a highly vascularised tumour generally treated with radiotherapy (RT). A recent preclinical study from our group  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.
KeywordsUveal melanoma IL-8 Angiogenesis VEGF
The authors declare that the experiments comply with the current laws of the country in which they were performed.
Conflict of interest
The authors declare that they have no conflict of interest.
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