Mesenchymal-epithelial Transition and Tumor Vascular Remodeling in Eribulin Chemotherapy for Breast Cancer
Mesenchymal-epithelial Transition and Tumor Vascular Remodeling in Eribulin Chemotherapy for Breast Cancer
复制标题
DOI：
10.21873/anticanres.12236
复制
发表时间：
2018-01-01
影响因子：
2
通讯作者：
Ohira, Masaichi
中科院分区：
文献类型：
--
作者：
Kashiwagi, Shinichiro;Asano, Yuka;Ohira, Masaichi
背景/目的：甲磺酸埃立布林目前用于局部晚期或转移性乳腺癌（MBC）的治疗。它是一种具有独特机制的细胞毒性药物，可抑制癌细胞的上皮-间质转化（EMT），促进肿瘤血管重塑。在本研究中，我们研究了在艾瑞布林治疗前后收集的临床标本中EMT和缺氧标志物的表达，以验证其独特的机制。患者与方法：采用免疫组织化学方法检测20例患者在艾瑞布林（n=10）或紫杉醇（n=10）化疗前后的MBC组织中EMT和细胞缺氧标志物[E-cadherin、n -cadherin、vimentin和碳酸酐酶9 (CA9)]的表达。结果：对伊瑞布林治疗有客观临床反应的患者的MBC组织中E-cadherin表达升高，CA9表达降低。e -cadherin阳性转化和ca9阴性转化患者的有效率（p=0.004和p=0.024）和治疗失败时间（p=0.018和p=0.038）均显著高于标志物表达无变化的患者。结论：伊瑞布林可抑制MBC患者临床标本中EMT和缺氧标志物的表达。结果提供了额外的临床数据，改善患者的生存与治疗的反应机制。
Background/Aim: Eribulin mesylate (eribulin) is currently used for the treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress the epithelial-mesenchymal transition (EMT) of cancer cells and promote tumor vascular remodeling. In this study, we investigated the expression of markers for EMT and hypoxia in sets of clinical specimens collected before and after eribulin treatment to verify its unique mechanisms. Patients and Methods: The expression of markers for EMT and cellular hypoxia [E-cadherin, N-cadherin, vimentin, and carbonic anhydrase 9 (CA9)] was examined immunohistochemically in MBC tissues collected from 20 patients before and after chemotherapy with either eribulin (n=10) or paclitaxel (n=10). Results: An increase of E-cadherin and decrease of CA9 expression were observed in MBC tissues from patients with objective clinical responses to eribulin treatment. Patients with E-cadherin-positive conversion and CA9-negative conversion had significantly higher response rates (p=0.004 and p=0.024, respectively) and prolonged time to treatment failure (p=0.018 and p=0.038, respectively) than patients without changes in marker expression. Conclusion: Expression of EMT and hypoxia markers in clinical samples from patients with MBC was suppressed by eribulin treatment. The results provide additional clinical data on improved survival of patients treated with eribulin and the mechanism of response.