Oxidative Stress in Malignant Melanoma Enhances Tumor Necrosis Factor-α Secretion of Tumor-Associated Macrophages That Promote Cancer Cell Invasion
Oxidative Stress in Malignant Melanoma Enhances Tumor Necrosis Factor-α Secretion of Tumor-Associated Macrophages That Promote Cancer Cell Invasion
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DOI：
10.1089/ars.2012.4617
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发表时间：
2013-10-20
影响因子：
6.6
通讯作者：
Shen, Pingping
中科院分区：
文献类型：
--
作者：
Lin, Xuzhu;Zheng, Wei;Shen, Pingping
目的：恶性黑色素瘤是众所周知的丰富的活性氧（ROS）存在于原发肿瘤的环境。在这种微环境中，肿瘤相关巨噬细胞（TAM）在肿瘤生长、侵袭和转移等肿瘤发展的多个步骤中发挥重要作用。因此，我们的目的是确定这种高水平的活性氧在原发性黑色素瘤是否能够促进肿瘤的侵袭性，通过影响TAM的性质。此外，我们希望进一步研究可能的潜在机制。结果：我们的特点是恶性黑色素瘤TAMs作为一个异质性表型，具有M1和M2标记。我们还揭示了高水平的细胞内ROS在增强TAMs的促侵袭签名中的作用，通过强烈增加它们的肿瘤坏死因子分泌，这可能归因于ROS增强的MAPK/ERK激酶1介导的过氧化物酶体增殖物激活受体（PPAR）易位。创新：这是第一项证明原发性黑色素瘤环境中高水平ROS可以影响TAM行为的研究。此外，我们也是第一个确定的核到细胞质易位的过氧化物酶体受体显着上调活性氧和负责的黑色素瘤TAM的proinvasiveness能力。结论：总之，我们的数据描述了高水平的ROS如何在增强恶性黑色素瘤中TAMs的促侵袭特性中发挥关键作用。抗氧化剂。氧化还原信号。19，1337-1355.
Aims: Malignant melanoma is well known for abundant reactive oxygen species (ROS) that exist in the primary tumor environment. Within this microenvironment, tumor-associated macrophages (TAMs) play substantial roles in multiple steps of tumor development in terms of tumor growth, invasion, and metastasis. We therefore aimed to determine whether this high-level ROS in primary melanoma is capable to promote tumor invasiveness by influencing TAM properties. Moreover, we wanted to further investigate probable underlying mechanisms. Results: We characterized malignant melanoma TAMs as a heterogeneous phenotype, which possesses both M1 and M2 markers. We also revealed a role for high-level intracellular ROS in enhancing proinvasion signature of TAMs by strongly increasing their tumor necrosis factor secretion, which is possibly attributed to ROS-enhanced peroxisome proliferator-activated receptor (PPAR) translocation mediated by MAPK/ERK kinase 1. Innovation: This is the first study demonstrating that high levels of ROS in the primary melanoma environment can influence TAM behaviors. Furthermore, we are also the first to indentify that nucleus-to-cytoplasm translocation of PPAR is significantly upregulated by ROS and responsible for the proinvasiveness capacity of melanoma TAMs. Conclusion: Taken together, our data describe how a high level of ROS plays a critical role in enhancing the proinvasion characteristic of TAMs in malignant melanoma. Antioxid. Redox Signal. 19, 1337-1355.