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CD90阳性细胞在食管鳞状细胞癌中表现出较强的放射抗性。

CD90 positive cells exhibit aggressive radioresistance in esophageal squamous cell carcinoma.

作者信息

Wang Yuandong, Zhang Chi, Zhu Hongcheng, Tang Junwei, Zhang Shu, Luo Jinhua, Sun Xinchen

机构信息

Department of Radiation Oncology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.

Liver Transplantation Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.

出版信息

J Thorac Dis. 2017 Mar;9(3):610-620. doi: 10.21037/jtd.2017.03.28.

Abstract

BACKGROUND

Cancer stem cells (CSCs) are widely abundant and considered to be an important factor in therapy resistance. They are also promising potential targets for conquering tumors. We explored the effects of radiation on stem cell-like tumor cells via the candidate marker CD90 to provide new ideas for the comprehensive treatment of esophageal squamous cell carcinoma (ESCC).

METHODS

We constructed CD90 overexpression ESCC cells by lentiviral transfection and observed differences of toxicity, proliferation, clone number, apoptosis, migration, invasion, and in vivo tumor formation after irradiation.

RESULTS

We found that the population of CD90 positive cells showed CSC-like characteristics, including increased tumorigenicity and migration in ESCC cells. We discovered that these capacities were strengthened to varying degrees in remaining cells after irradiation. Further exploration revealed that the genes of ETS-1 and its downstream target MMPs changed significantly, which are correlated with the epithelial mesenchymal transition (EMT). These effects lead to enhanced tumor growth and resistance to radiation.

CONCLUSIONS

We show that CD90 overexpressing ESCC cells exhibit CSC-like characteristics and radiation resistance. From a clinical perspective, ESCC patients with tumors that have high CD90 expression, which inhibits apoptosis, could exhibit more local invasion as well as distant metastasis, indicating a poorer prognosis. Research on the mechanism of CD90 may provide a new perspective to therapeutic strategies for patients with ESCC.

摘要

背景

癌症干细胞(CSCs)广泛存在,被认为是治疗耐药的重要因素。它们也是攻克肿瘤的潜在有希望的靶点。我们通过候选标志物CD90探讨辐射对干细胞样肿瘤细胞的影响,为食管鳞状细胞癌(ESCC)的综合治疗提供新思路。

方法

我们通过慢病毒转染构建CD90过表达的ESCC细胞,并观察照射后毒性、增殖、克隆数、凋亡、迁移、侵袭及体内肿瘤形成的差异。

结果

我们发现CD90阳性细胞群体表现出CSC样特征,包括ESCC细胞中致瘤性和迁移增加。我们发现照射后剩余细胞中这些能力不同程度增强。进一步探索发现ETS-1及其下游靶点MMPs的基因发生显著变化,这与上皮-间质转化(EMT)相关。这些效应导致肿瘤生长增强和辐射抗性。

结论

我们表明CD90过表达的ESCC细胞表现出CSC样特征和辐射抗性。从临床角度看,CD90高表达抑制凋亡的ESCC患者肿瘤可能表现出更多局部侵袭以及远处转移,提示预后较差。对CD90机制的研究可能为ESCC患者的治疗策略提供新视角。

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