Laboratory of Molecular Pathology, State University of Londrina, Brazil; Laboratory of Pathophysiology and Free Radicals, State University of Londrina, Brazil; ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany.
Laboratory of Molecular Pathology, State University of Londrina, Brazil; Laboratory of Tissue Microenvironment, Federal University of Minas Gerais, Brazil.
Pathol Res Pract. 2020 Nov;216(11):153218. doi: 10.1016/j.prp.2020.153218. Epub 2020 Sep 23.
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.
恶性黑色素瘤是最危险的皮肤癌形式。尽管有新的黑色素瘤治疗方法，但有效的治疗主要受到过度转移的限制。目前，决定转移发展的因素尚不清楚，但氧化应激被认为与之有关。为此，我们使用同源 B16F10 黑色素瘤模型分析了转移发展过程中的氧化应激参数。在疾病的最早阶段，血浆脂质过氧化增加，氧化损伤逐渐减少，抗氧化防御增加。相反，在整个疾病过程中，转移性结节中观察到脂质过氧化和 3-硝基酪氨酸增加，抗氧化参数减少。这与血管内皮生长因子和增殖细胞核抗原的逐渐增加同时发生。我们得出结论，在转移过程中，血液中的氧化应激会降低，而在肿瘤微环境中转移性结节的增殖和生长过程中，硝化应激会增加。这些结果将有助于更好地了解氧化应激在黑色素瘤转移中的作用。
