The progression of metastatic melanoma augments a pro-oxidative milieu locally but not systemically.

ABSTRACT

Malignant melanoma is the most dangerous form of skin cancer. Despite new therapies for melanoma treatment, effective therapy is mainly limited by excessive metastasis. Currently, the factors determining metastasis development are not elucidated, but oxidative stress was suggested to be involved. To this end, we analyzed oxidative stress parameters during the metastatic development using the syngeneic B16F10 melanoma model. An increase in blood plasma lipid peroxidation occurred at the earliest stage of the disease, with a progressive decrease in oxidative damage and an increase in antioxidant defense. Vice versa, increased lipid peroxidation and 3-nitrotyrosine, and decreased antioxidant parameters were observed in the metastatic nodules throughout the disease. This was concomitant with a progressive increase in vascular endothelial growth factor and proliferating cell nuclear antigen. We conclude that the oxidative stress in the bloodstream decreases during the metastatic process and that nitrosative stress increases during the proliferation and growth of metastatic nodules in the tumor microenvironment. These results will help to better understand the role of oxidative stress during melanoma metastasis.