Kong Peng, Pan Hong, Yu Muxin, Chen Lie, Ge Han, Zhu Jin, Ma Ge, Li Li, Ding Qiang, Zhou Wenbin, Wang Shui
Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 210029 Nanjing, China.
Oncotarget. 2017 Dec 1;8(70):115089-115101. doi: 10.18632/oncotarget.22859. eCollection 2017 Dec 29.
Microwave ablation (MWA), a thermal ablation, is an effective treatment for breast cancer. However, residual breast cancer is still detected. The biological characteristics of residual breast cancer after thermal ablation remain unknown. To mimic insufficient MWA , breast cancer cells were treated at 37°C, 42°C, 45°C, 47°C and 50°C for 10 mins, the 37°C as control group. Insufficient MWA induced EMT-like changes of residual breast cancer by down-regulation of E-cadherin and up-regulation of vimentin and N-cadherin and . For the first time, we reported insufficient MWA promoted distant metastasis of residual breast cancer . Reduced β-catenin expression by siRNA diminished the EMT-like phenotype and enhanced migration capability induced by heat treatment in breast cancer cells. Moreover, ICG001, a special inhibitor of β-catenin pathway, depressed EMT of residual tumor and distant metastasis in an insufficient MWA nude mice model of breast cancer. In conclusion, our results demonstrate that insufficient MWA promotes EMT of residual breast cancer by activating β-catenin signal pathway, resulting in enhanced distant metastasis of residual breast cancer. In addition, the effectiveness of ICG001 in suppressing enhanced metastasis of residual breast cancer is preliminarily validated.
微波消融(MWA)是一种热消融技术,是治疗乳腺癌的有效方法。然而,仍可检测到残留的乳腺癌。热消融后残留乳腺癌的生物学特性尚不清楚。为模拟不完全微波消融,将乳腺癌细胞分别在37℃、42℃、45℃、47℃和50℃处理10分钟,其中37℃为对照组。不完全微波消融通过下调E-钙黏蛋白、上调波形蛋白和N-钙黏蛋白诱导残留乳腺癌发生上皮-间质转化样改变。我们首次报道不完全微波消融促进残留乳腺癌的远处转移。通过小干扰RNA降低β-连环蛋白表达可减轻热处理诱导的乳腺癌细胞上皮-间质转化样表型并增强其迁移能力。此外,β-连环蛋白信号通路的特异性抑制剂ICG001可抑制乳腺癌不完全微波消融裸鼠模型中残留肿瘤的上皮-间质转化及远处转移。总之,我们的结果表明,不完全微波消融通过激活β-连环蛋白信号通路促进残留乳腺癌的上皮-间质转化,导致残留乳腺癌远处转移增加。此外,初步验证了ICG001在抑制残留乳腺癌转移增强方面的有效性。