Effect of a hypoxic microenvironment after radiofrequency ablation on residual hepatocellular cell migration and invasion.
Effect of a hypoxic microenvironment after radiofrequency ablation on residual hepatocellular cell migration and invasion.
复制标题
射频消融后缺氧微环境对残留肝细胞迁移和侵袭的影响
DOI：
10.1111/cas.13191
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发表时间：
2017-04
期刊：
影响因子：
5.7
通讯作者：
Luo B
中科院分区：
文献类型：
--
作者：
Tong Y;Yang H;Xu X;Ruan J;Liang M;Wu J;Luo B
临床观察表明，肿瘤消融的边界往往小于安全边界，射频消融（RFA）治疗肝细胞癌（HCC）可能加速其复发和转移。RFA可导致在正常肝组织和坏死凝血之间形成过渡区，其中血液停滞和血栓形成将残留癌细胞暴露于缺氧微环境。随着阻塞血管的缓慢再灌注，氧气供应逐渐恢复。这里，HCC细胞经历热处理并在缺氧条件下培养以模拟上述情况，并在存活细胞中观察形态学变化。与它们的亲本细胞相比，缺氧HCC细胞表现出包括增强的侵袭、转移和化疗耐药能力以及间充质特征的变化。干细胞样细胞的比例也更高。然而，无论是改善缺氧微环境还是沉默缺氧诱导因子（HIF）-1 α信号转导，都显著降低了侵袭、转移和化疗耐药的可能性，并在不同程度上逆转了上皮-间质转化。总之，这些结果表明，RFA后持续的缺氧微环境可能对HCC患者的预后产生负面影响，最大限度地减少暴露于缺氧微环境和靶向HIF-1α信号传导可能是RFA治疗不足的患者的有效策略。
Clinical observations have shown that the boundary of tumor ablation is often less than safe border and that the use of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) may probably accelerate its recurrence and metastasis. RFA can cause the formation of a transition zone between normal liver tissues and necrotic coagulation, where blood stagnation and thrombosis expose residual cancer cells to a hypoxic microenvironment. As the blocked vessels are slowly reperfused, the oxygen supply is gradually restored. Here, HCC cells underwent heat treatment and were cultured under hypoxic conditions to mimic the aforementioned situation, and morphological changes were observed in the surviving cells. Compared with their parental cells, hypoxic HCC cells showed changes that include enhanced invasive, metastatic, and chemoresistant abilities as well as mesenchymal characteristics. There was also a higher percentage of stem‐like cells. However, either improving the hypoxic microenvironment or silencing hypoxia inducible factor (HIF)‐1α signaling significantly reduced the invasive, metastatic, and chemoresistant potential and reversed the epithelial‐mesenchymal transition to varying degrees. Together, these results indicated that a sustained hypoxic microenvironment after RFA may exert a negative impact on the prognosis of HCC patients, and minimizing exposure to a hypoxic microenvironment and targeting HIF‐1α signaling might be effective strategies for patients who experience insufficient RFA therapy.