Oxidative stress in malignant melanoma and non-melanoma skin cancer
Oxidative stress in malignant melanoma and non-melanoma skin cancer
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DOI：
10.1046/j.1365-2133.2003.05303.x
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发表时间：
2003-05-01
影响因子：
10.3
通讯作者：
Thiele, JJ
中科院分区：
文献类型：
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作者：
Sander, CS;Hamm, F;Thiele, JJ
背景太阳紫外线（UV）辐射被认为是黑色素瘤和非黑色素瘤皮肤癌的主要病因。越来越多的证据表明，氧化应激参与光致癌作用。然而，人体皮肤的体内数据仍然缺乏。活性氧参与了许多病理生理过程，包括DNA损伤和脂质过氧化（LPO），并被认为是肿瘤进展的关键因素。目的我们假设，在人类皮肤癌的自然氧化还原平衡被打乱，这种不平衡可能导致LPO产品的积累。将浅表扩散性黑色素瘤的皮肤活检与年龄匹配的良性黑色素细胞痣和年轻健康对照进行比较。此外，还研究了非黑色素瘤皮肤癌（基底细胞癌、鳞状细胞癌）和光化性角化病（各n = 18）。抗氧化酶，铜锌超氧化物歧化酶，锰超氧化物歧化酶和过氧化氢酶的表达进行了分析，免疫组织化学技术。为了检测LPO产品，蛋白质结合的丙二醛（MDA）visualized.Results在人类黑色素瘤活检，一个显着的过度表达的抗氧化酶被发现时，与周围的非肿瘤组织，良性黑色素细胞痣，和年轻的控制。有趣的是，黑色素瘤组织中LPO标记物MDA显著增加。MDA不仅存在于典型的黑色素瘤细胞中，也存在于周围的角质形成细胞中。相比之下，一个严重干扰的抗氧化平衡减少抗氧化酶被发现在非黑色素瘤肿瘤，而MDA升高，只有在鳞状细胞cancer.Conclusions这些研究结果表明，氧化应激可能发挥不同的作用，在人类皮肤癌的发病机制。在非黑色素瘤皮肤癌中，由慢性紫外线暴露引起的抗氧化防御减弱可能有助于多步致癌，而黑色素瘤细胞表现出增加的氧化应激，这可能会损害周围组织，从而支持转移的进展。
Background Solar ultraviolet (UV) radiation is considered to be a major aetiological factor in melanoma and non-melanoma skin cancer. A growing body of evidence indicates that oxidative stress is involved in photocarcinogenesis. However, in vivo data for human skin are still lacking. Reactive oxygen species participate in a number of pathophysiological processes including DNA damage and lipid peroxidation (LPO) and are considered to be a key factor in tumour progression.Objectives We hypothesized that in human skin cancer the natural redox balance is disturbed and that this imbalance may result in an accumulation of LPO products.Methods To test this, skin biopsies of superficial spreading melanoma were compared with age-matched benign melanocytic naevi and young healthy controls. Additionally, non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma) and actinic keratosis were investigated (n = 18 each). Expression of the antioxidant enzymes, copper-zinc superoxide dismutase, manganese superoxide dismutase and catalase was analysed by immunohistochemical techniques. To detect LPO products, protein-bound malondialdehyde (MDA) was visualized.Results In human melanoma biopsies, a significant overexpression of the antioxidant enzymes was found when compared with surrounding non-tumour tissue, benign melanocytic naevi, and young controls. Intriguingly, the LPO marker MDA was significantly increased in melanoma tissue. MDA was located not only in typical melanoma cells, but also occurred in surrounding keratinocytes. In contrast, a severely disturbed antioxidant balance with diminished antioxidant enzymes was found in non-melanoma tumours, whereas MDA was elevated only in squamous cell carcinomas.Conclusions These findings indicate that oxidative stress may play different roles in the pathogenesis of human skin cancers. In non-melanoma skin cancer, a diminished antioxidant defence caused by chronic UV exposure might contribute to multistep carcinogenesis, whereas melanoma cells exhibit increased oxidative stress which could damage surrounding tissue and thus support the progression of metastasis.