Unraveling the human protein atlas of metastatic melanoma in the course of ultraviolet radiation-derived photo-therapy.

Unlabelled: To explore the photo-therapeutic capacity of UV radiation in solid tumors, we herein employed an nLC-MS/MS technology to profile the proteomic landscape of irradiated WM-266-4 human metastatic-melanoma cells. Obtained data resulted in proteomic catalogues of 5982 and 7280 proteins for UVB- and UVC-radiation conditions, respectively, and indicated the ability of UVB/C-radiation forms to eliminate metastatic-melanoma cells through induction of synergistically operating programs of apoptosis and necroptosis. However, it seems that one or more WM-266-4 cell sub-populations may escape from UV-radiation's photo-damaging activity, acquiring, besides apoptosis tolerance, an EMT phenotype that likely offers them the advantage of developing resistance to certain chemotherapeutic drugs. Low levels of autophagy may also critically contribute to the selective survival and growth of UV-irradiated melanoma-cell escapers. These are the cells that must be systemically targeted with novel therapeutic schemes, like the one of UV radiation and Irinotecan herein suggested to be holding strong promise for the effective treatment of metastatic-melanoma patients. Given the dual nature of UV radiation to serve as both anti-tumorigenic and tumorigenic agent, all individuals being subjected to risk factors for melanoma development have to be appropriately informed and educated, in order to integrate the innovative PPPM concept in their healthcare-sector management.

Significance: This study reports the application of nLC-MS/MS technology to deeply map the proteomic landscape of UV-irradiated human metastatic-melanoma cells. Data bioinformatics processing led to molecular-network reconstructions that unearthed the dual nature of UV radiation to serve as both anti-tumorigenic and tumorigenic factor in metastatic-melanoma cellular environments. Our UV radiation-derived "photo-proteomic" atlas may prove valuable for the identification of new biomarkers and development of novel therapies for the disease. Given that UV radiation represents a major risk factor causing melanoma, a PPPM-based life style and clinical practice must be embraced by all individuals being prone to disease's appearance and expansion.