Yan Yong-Rong, Xie Qiang, Li Feng, Zhang Yong, Ma Ji-Wei, Xie Si-Ming, Li Hai-Ying, Zhong Xue-Yun
Department of Pathology, Medical School of Jinan University, Guangzhou, China.
Neuropathology. 2014 Apr;34(2):128-34. doi: 10.1111/neup.12062. Epub 2013 Sep 22.
Chemotherapy has been considered as an effective treatment for malignant glioma; however, it becomes increasingly ineffective with tumor progression. Epithelial-to-mesenchymal transition (EMT) is a process whereby cells acquire morphologic and molecular alterations that facilitate tumor metastasis and progression. Emerging evidence associates chemoresistance with the acquisition of EMT in cancer. However, it is not clear whether this phenomenon is involved in glioma. We used the previously established human glioma cell lines SWOZ1, SWOZ2 and SWOZ2-BCNU to assess cellular morphology, molecular changes, migration and invasion. We found that BCNU-resistant cells showed multiple drug resistance and phenotypic changes consistent with EMT, including spindle-shaped morphology and enhanced pseudopodia formation. Decreased expression of the epithelial adhesion molecule E-cadherin and increased expression of the mesenchymal marker vimentin were observed in BCNU-resistant SWOZ1 and SWOZ2-BCNU cells compared to SWOZ2 cells. Migratory and metastatic potentials were markedly enhanced in SWOZ1 and SWOZ2-BCNU cells compared to SWOZ2 cells. These data suggest that there is a possible link between drug resistance and EMT induction in glioma cells. Gaining further insight into the mechanisms underlying chemoresistance and EMT may enable the restoration of chemosensitivity or suppression of metastasis.
化疗一直被认为是治疗恶性胶质瘤的有效方法；然而，随着肿瘤进展，其效果越来越差。上皮-间质转化（EMT）是一个细胞获得形态和分子改变从而促进肿瘤转移和进展的过程。新出现的证据表明癌症中的化疗耐药性与EMT的获得有关。然而，尚不清楚这种现象是否与胶质瘤有关。我们使用先前建立的人胶质瘤细胞系SWOZ1、SWOZ2和SWOZ2-BCNU来评估细胞形态、分子变化、迁移和侵袭。我们发现，对卡莫司汀（BCNU）耐药的细胞表现出多药耐药性和与EMT一致的表型变化，包括纺锤形形态和伪足形成增强。与SWOZ2细胞相比，在对BCNU耐药的SWOZ1和SWOZ2-BCNU细胞中观察到上皮粘附分子E-钙粘蛋白表达降低，间充质标志物波形蛋白表达增加。与SWOZ2细胞相比，SWOZ1和SWOZ2-BCNU细胞的迁移和转移潜能明显增强。这些数据表明胶质瘤细胞中的耐药性与EMT诱导之间可能存在联系。进一步深入了解化疗耐药性和EMT的潜在机制可能会恢复化疗敏感性或抑制转移。
