Effect of eribulin on epithelial-mesenchymal transition plasticity in metastatic breast cancer: An exploratory, prospective study
Effect of eribulin on epithelial-mesenchymal transition plasticity in metastatic breast cancer: An exploratory, prospective study
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DOI：
10.1111/gtc.13019
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发表时间：
2023-03-12
期刊：
影响因子：
2.1
通讯作者：
Utsumi，Toshiaki
中科院分区：
文献类型：
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作者：
Hayashi，Takanori;Kobayashi，Naomi;Utsumi，Toshiaki
上皮-间质转化（EMT）在癌症转移和治疗抵抗中发挥着关键作用，从而使预后恶化。在 III 期试验中，艾日布林改善了转移性乳腺癌 (MBC) 患者的总生存期。在临床前研究中，艾日布林抑制 EMT。然而，关于使用艾日布林治疗 MBC 患者的临床数据有限。在这项探索性、前瞻性研究中，我们研究了艾日布林对 MBC 患者 EMT 的影响。 22 名年龄在 44-82 岁的复发性乳腺癌或 MBC 患者接受了艾日布林治疗。在治疗前和第一个艾日布林治疗周期的第 15±5 天获取乳腺癌组织样本。使用蛋白质印迹法分析 EMT 标记物（E-钙粘蛋白、密蛋白-3、波形蛋白和 N-钙粘蛋白）。根据单个肿瘤治疗前后上皮细胞与间质细胞标志物的比率来评估 EMT 变化。治疗后 E-钙粘蛋白/波形蛋白、紧密蛋白-3/波形蛋白、E-钙粘蛋白/N-钙粘蛋白和紧密蛋白-3/N-钙粘蛋白比率显着升高（分别为 p= .007、p= .005、p= .006 和 p= .011）。基于E-钙粘蛋白/波形蛋白，65.0%的肿瘤转变为上皮表型，而基于claudin-3/波形蛋白的肿瘤转变为上皮表型为66.7%，基于E-钙粘蛋白/N-钙粘蛋白的肿瘤转变为84.6%，基于claudin-3/N-钙粘蛋白比率的肿瘤转变为上皮表型为71.4%。因此，我们的结果表明艾日布林抑制乳腺癌组织中的 EMT。
Epithelial–mesenchymal transition (EMT) plays a pivotal role in cancer metastasis and treatment resistance, which worsens prognosis. In phase III trials, eribulin improved overall survival in metastatic breast cancer (MBC) patients. In preclinical studies, eribulin suppressed EMT. However, clinical data on the use of eribulin for MBC patients are limited. In this exploratory, prospective study, we examined the effect of eribulin on EMT in MBC patients. Twenty‐two patients aged 44–82 years with recurrent breast cancer or MBC were treated with eribulin. Breast cancer tissue samples were obtained before treatment and on Day 15 ± 5 of the first cycle of eribulin treatment. EMT markers (E‐cadherin, claudin‐3, vimentin, and N‐cadherin) were analyzed using western blotting. EMT changes were evaluated based on the ratio of epithelial to mesenchymal markers before and after treatment in individual tumors. E‐cadherin/vimentin, claudin‐3/vimentin, E‐cadherin/N‐cadherin, and claudin‐3/N‐cadherin ratios were significantly higher after treatment (p= .007,p= .005,p= .006, andp= .011, respectively). Based on E‐cadherin/vimentin, 65.0% of tumors shifted to an epithelial phenotype, as compared to 66.7% based on claudin‐3/vimentin, 84.6% based on E‐cadherin/N‐cadherin, and 71.4% based on claudin‐3/N‐cadherin ratios. Thus, our results showed that eribulin suppressed EMT in breast cancer tissues.