Institute for Biological Research "Sinisa Stankovic" - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Redox Biol. 2021 May;41:101939. doi: 10.1016/j.redox.2021.101939. Epub 2021 Mar 16.
One of the underlying mechanisms that could link breast cancer and obesity is shifted redox homeostasis in the tumor microenvironment. To reveal the relationship between the malignant phenotype and obesity, we compared redox profiles of breast tumor and tumor-associated adipose tissue from premenopausal women: normal-weight with benign tumors, overweight/obese with benign tumors, normal-weight with malignant tumors, and overweight/obese with malignant tumors. Namely, we examined the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression and activity of main antioxidant defense (AD) enzymes: copper, zinc- and manganese superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of 4-hydroxy-2-nonenal (4-HNE) modified proteins. Higher protein expression and activity of AD enzymes were found in malignant tumor tissue than benign tumor tissue, irrespective of obesity. Nevertheless, malignant tumor tissue of overweight/obese women was characterized by higher protein expression of Nrf2 and weaker immunopositivity for 4-HNE modified proteins. In malignant tumor-associated adipose tissue, the redox profile was clearly related to obesity. Higher Nrf2 protein expression and higher AD enzyme levels were observed in normal-weight women, while stronger immunopositivity for 4-HNE modified proteins was found in overweight/obese women. The results suggest that the complex interplay between obesity and malignancy involves redox-sensitive pathways in breast tumor and tumor-associated adipose tissue.
一种可能将乳腺癌和肥胖联系起来的潜在机制是肿瘤微环境中氧化还原稳态的改变。为了揭示恶性表型与肥胖之间的关系，我们比较了绝经前女性的乳腺肿瘤和肿瘤相关脂肪组织的氧化还原谱：正常体重伴良性肿瘤、超重/肥胖伴良性肿瘤、正常体重伴恶性肿瘤和超重/肥胖伴恶性肿瘤。即，我们检查了核因子红细胞 2 相关因子 2（Nrf2）的蛋白表达、主要抗氧化防御（AD）酶的蛋白表达和活性：铜、锌和锰超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶，以及 4-羟基-2-壬烯醛（4-HNE）修饰蛋白的水平。无论肥胖与否，恶性肿瘤组织中的 AD 酶蛋白表达和活性均高于良性肿瘤组织。然而，超重/肥胖女性的恶性肿瘤组织表现为 Nrf2 蛋白表达更高，4-HNE 修饰蛋白的免疫阳性较弱。在恶性肿瘤相关脂肪组织中，氧化还原谱明显与肥胖有关。在正常体重女性中观察到更高的 Nrf2 蛋白表达和更高的 AD 酶水平，而超重/肥胖女性则发现更强的 4-HNE 修饰蛋白免疫阳性。结果表明，肥胖和恶性肿瘤之间的复杂相互作用涉及乳腺肿瘤和肿瘤相关脂肪组织中的氧化还原敏感途径。
