Abstract
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 in vitro, 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 in vitro and in vivo. For the first time, we reported insufficient MWA promoted distant metastasis of residual breast cancer in vivo. 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.
Highlights
Microwave ablation (MWA), a minimally invasive therapy, presents the advantages of higher ablation temperature, larger ablation range and shorter ablation time compared with other thermal ablations such as radiofrequency ablation (RFA), high-intensity focused ultrasound and laser ablation in the treatment of solid tumors [1,2,3]
To mimic insufficient MWA in vitro, SUM-1315, ZR-75-1 breast cancer cells were treated at 37°C, 42°C, 45°C, 47°C and 50°Cfor 10mins, the 37°C as the control group
Residual tumor and local recurrence are the main problems in the treatment of solid tumors with thermal ablation
Summary
Microwave ablation (MWA), a minimally invasive therapy, presents the advantages of higher ablation temperature, larger ablation range and shorter ablation time compared with other thermal ablations such as radiofrequency ablation (RFA), high-intensity focused ultrasound and laser ablation in the treatment of solid tumors [1,2,3]. The efficiency and security of MWA in the treatment of breast cancer have been confirmed in our previous studies [4,5,6]; residual tumor has been found in several patients and animal models after MWA. Residual tumor and local recurrence after thermal ablation are the great challenge of these minimally invasive treatments. In hepatocelluar carcinoma (HCC) [9,10,11], the local recurrence after RFA shows a more malignant phenotype with raised tumor growth and distant metastasis. To the best of our knowledge, there have been no reports on biological characteristics changes of residual breast cancer after thermal ablation
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