UVA-Irradiation Induces Melanoma Invasion via the Enhanced Warburg Effect
UVA-Irradiation Induces Melanoma Invasion via the Enhanced Warburg Effect
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DOI：
10.1016/j.jid.2016.02.815
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发表时间：
2016-09-01
影响因子：
6.5
通讯作者：
Berneburg, Mark
中科院分区：
文献类型：
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作者：
Kamenisch, York;Baban, Tarza S. A.;Berneburg, Mark
黑色素瘤是一种恶性肿瘤，其中UVA（320-400 nm）辐射被认为是一个重要的风险因素。但是UVA在黑色素瘤向侵袭性表型发展中的作用仍然没有得到充分的研究。对于大多数增殖的肿瘤细胞，有氧糖酵解的偏好被描述为瓦尔堡效应。在这里，我们调查的影响UVA照射的变化，在瓦尔堡效应和肿瘤进展的侵袭潜力。在UVA照射下，来自初始肿瘤的黑色素瘤细胞系显示出瓦尔堡效应的诱导，葡萄糖消耗和乳酸产生增加，这至少部分地由活性氧介导。与UVA治疗和增强的乳酸产生相关，肿瘤相关蛋白酶和原位侵袭上调。同时，UVA增加了细胞内进展标志物转酮醇酶和活化蛋白激酶Akt的浓度，两者都参与了随着增殖而增加的代谢变化。使用入侵检测，我们表明，乳酸，从UVA增强和部分活性氧介导的瓦尔堡效应，增加了所有黑色素瘤细胞系的侵袭潜力的调查。因此，我们证明了在黑色素瘤细胞中，由UVA照射诱导的乳酸的产生通过表达肿瘤相关蛋白酶来增加黑色素瘤细胞的侵袭性。
Melanoma is a malignant tumor in which UVA (320-400 nm) radiation is considered to be an important risk factor. But the role of UVA in melanoma progression toward an invasive phenotype is still not adequately investigated. For most proliferating tumor cells the preference of aerobic glycolysis has been described as the Warburg effect. Here we investigate the effect of UVA irradiation on changes in the Warburg effect and tumor progression toward invasive potential. On UVA irradiation, melanoma cell lines from initial tumors show an induction of the Warburg effect with increased glucose consumption and lactate production, which is at least partially mediated by reactive oxygen species. Associated with UVA treatment and enhanced lactic acid production, tumor-relevant proteases and in situ invasion is upregulated. Simultaneously, UVA increases intracellular concentrations of progression marker transketolase and activated protein kinase Akt, both involved in metabolic changes that increase with proliferation. Using invasion assays we show that lactic acid, resulting from the UVA enhanced and partially reactive oxygen species-mediated Warburg effect, increases the invasive potential of all melanoma cell lines investigated. Therefore, we demonstrate in melanoma cells that production of lactic acid, induced by UVA irradiation, increases invasiveness of melanoma cells via expression of tumor-relevant proteases.