SO2 derivatives and As co-exposure promote liver cancer metastasis through integrin αvβ3 activation
SO2 derivatives and As co-exposure promote liver cancer metastasis through integrin αvβ3 activation
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DOI：
10.1016/j.ecoenv.2019.06.029
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发表时间：
2019-10-15
影响因子：
6.8
通讯作者：
Yi, Huilan
中科院分区：
文献类型：
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作者：
Ji, Pengyu;Li, Zhuoyu;Yi, Huilan
砷(As)和二氧化硫(SO2)是两种已被证明促进人类癌症发展的环境污染物。近年来，由于污染加剧，除砷外，人类还经常接触到SO2。尽管制定和实施了环境和空气质量标准，但由砷或二氧化硫引起的疾病病例继续以惊人的速度上升。目前尚不清楚同时接触砷和二氧化硫是否会导致促癌活性增加。在本研究中，砷和二氧化硫的浓度低于世界卫生组织制定的现行环境标准(砷浓度应低于1×10(-2)mg/L，二氧化硫浓度应低于50微克/立方米(3))，以细胞为基础的方法研究砷和二氧化硫可能的长期协同效应。我们发现，共同暴露在这些污染物中显著促进了HepG2癌细胞的迁移，而单独接触As或SO2没有显著的影响。整合素αvβ3在这一过程中起着关键作用，因为整合素αvβ3抑制剂cilengiide实质上阻止了AS和SO2诱导的细胞迁移。基质金属蛋白酶、IL-8和转化生长因子-β也参与了诱导细胞迁移。综上所述，AS和SO2联合暴露促进了整合素依赖的细胞迁移，并可能与激活肝癌进展的机制有关。
Arsenic (As) and sulfur dioxide (SO2) are two environmental pollutants that have been shown to promote the development of human cancer. In recent years, due to increased pollution, humans are often exposed to SO2, in addition to As. Despite the development and implementation of standards for environment and air quality, cases of disease caused by As or SO2 continue to rise alarmingly. It is currently unknown whether simultaneous exposure to As and SO2 results in increased cancer promoting activity. In this study, concentrations of As and SO2 below the limits established by the world health organization (WHO) in force environmental standards (concentrations of As should be lower than 1x10(-2) mg/L and SO2 should be lower than 50 mu g/m(3)), were employed to investigate possible, long-term, synergistic effects of As and SO2, by using cell-based assays. We found that co-exposure to these pollutants significantly promotes HepG2 cancer cell migration, while As or SO2 alone have no remarkable effects. Integrins alpha v beta 3 play a key role in this process, as cilengitide, an integrin alpha v beta 3 inhibitor, substantially prevented As and SO2-induced cell migration. MMPs, IL-8, and TGF-beta were also involved in the induced cell migration. In summary, combined exposure to As and SO2 promotes integrin-dependent cell migration and may be of relevance for the activation of mechanisms underlying liver cancer progression.