Hypoxia and hydrogen sulfide differentially affect normal and tumor-derived vascular endothelium.
Hypoxia and hydrogen sulfide differentially affect normal and tumor-derived vascular endothelium.
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DOI：
10.1016/j.redox.2017.03.015
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发表时间：
2017-08
期刊：
影响因子：
11.4
通讯作者：
Munaron L
中科院分区：
文献类型：
--
作者：
Bianco S;Mancardi D;Merlino A;Bussolati B;Munaron L
内皮细胞在生理和病理条件下的血管形成中起关键作用。它们的行为受包括气体递质（H2S、NO和CO）在内的血液成分的影响。肿瘤细胞经历促氧化和缺氧状态之间的循环转换，在这种情况下，H2S可以是细胞保护性的，也可以是有害的，这取决于其浓度。H2S对肿瘤发生和发展的影响研究很少，特别是关于肿瘤血管生成的研究。我们以前证明，H2S是促血管生成的肿瘤，但不是正常的内皮细胞，这可能是一个目标的抗血管生成治疗策略。在这项工作中，我们研究了在氧化应激、缺氧和外源性H2S处理下，与正常微血管内皮（HMEC）相比，来自两种不同肿瘤（乳腺癌和肾癌（BTEC和RTEC））的人EC的细胞活力、迁移和小管形成。所有EC类型对过氧化氢诱导的氧化应激都类似地敏感;化学缺氧差异性地影响内皮存活力，其结果不被真实的缺氧改变。H2S既不影响细胞活力，也不防止缺氧和H2 O2诱导的损伤。内皮细胞迁移是由缺氧增强，而肾小管生成抑制所有EC类型。H2S对EC迁移和小管发生的作用不同。这些数据提供了正常和改变的内皮响应于环境条件的很大变化性的证据。
endothelial cells play a key role in vessels formation both under physiological and pathological conditions. Their behavior is influenced by blood components including gasotransmitters (H2S, NO and CO). Tumor cells are subjected to a cyclic shift between pro-oxidative and hypoxic state and, in this scenario, H2S can be both cytoprotective and detrimental depending on its concentration. H2S effects on tumors onset and development is scarcely studied, particularly concerning tumor angiogenesis. We previously demonstrated that H2S is proangiogenic for tumoral but not for normal endothelium and this may represent a target for antiangiogenic therapeutical strategies. in this work, we investigate cell viability, migration and tubulogenesis on human EC derived from two different tumors, breast and renal carcinoma (BTEC and RTEC), compared to normal microvascular endothelium (HMEC) under oxidative stress, hypoxia and treatment with exogenous H2S. all EC types are similarly sensitive to oxidative stress induced by hydrogen peroxide; chemical hypoxia differentially affects endothelial viability, that results unaltered by real hypoxia. H2S neither affects cell viability nor prevents hypoxia and H2O2-induced damage. Endothelial migration is enhanced by hypoxia, while tubulogenesis is inhibited for all EC types. H2S acts differentially on EC migration and tubulogenesis. these data provide evidence for a great variability of normal and altered endothelium in response to the environmental conditions.