Identification and characterization of slow-cycling cells in Ewing sarcoma
Identification and characterization of slow-cycling cells in Ewing sarcoma
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DOI：
10.3892/ijo.2022.5428
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发表时间：
2022-09
影响因子：
5.2
通讯作者：
S. Yahiro;Teruya Kawamoto;Shuichi Fujiwara;H. Hara;N. Fukase;Ryoko Sawada;Toshiyuki Takemori;T. Miyamo
中科院分区：
文献类型：
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作者：
S. Yahiro;Teruya Kawamoto;Shuichi Fujiwara;H. Hara;N. Fukase;Ryoko Sawada;Toshiyuki Takemori;T. Miyamo
尤文肉瘤(ES)是一种侵袭性的原发恶性骨肿瘤，主要影响儿童和年轻人。多模式治疗显著提高了局限性ES患者的存活率。然而，治疗后的局部复发和远处转移仍然是ES患者的主要担忧。最近的研究表明，慢周期细胞(SCCs)与肿瘤的进展、局部复发和远处转移有关。根据这些研究的结果，推测干细胞可能在ES患者的肿瘤进展、化疗耐药和局部/远端复发中发挥关键作用。本研究应用标记保留系统使用羧基荧光素二乙酸酯琥珀酰亚胺酯(CFSE)来鉴定和分离ES细胞系中的SCCs。此外，还比较了SCCs与非SCCs的球体形成能力、细胞周期分布和化疗耐药性等特性。RNA测序还发现，与非鳞状细胞癌相比，鳞状细胞癌中有几个基因表达上调，这些基因不仅抑制了细胞周期进程，而且促进了鳞状细胞癌的恶性特性。总体而言，本研究通过使用CFSE的标记保留系统成功地鉴定了ES细胞中的干细胞。此外，据我们所知，本研究首次描述了胚胎干细胞的特征特性。这项研究的发现，如果得到证实，可能被证明是有用的，以阐明潜在的分子机制和确定有效的治疗靶点为ES。
Ewing sarcoma (ES) is an aggressive primary malignant bone tumor that predominantly affects children and young adults. Multimodal treatment approaches have markedly improved the survival of patients with localized ES. However, local recurrence and distant metastasis following curative therapies remain a main concern for patients with ES. Recent studies have suggested that slow-cycling cells (SCCs) are associated with tumor progression, local recurrence and distant metastasis in various types of cancers. According to the results of these studies, it was hypothesized that SCCs may play a critical role in tumor progression, chemoresistance and local/distal recurrence in patients with ES. The present study applied a label-retaining system using carboxyfluorescein diacetate succinimidyl ester (CFSE) to identify and isolate SCCs in ES cell lines. In addition, the properties of SCCs, including sphere formation ability, cell cycle distribution and chemoresistance, in comparison with non-SCCs were investigated. RNA sequencing also revealed several upregulated genes in SCCs as compared with non-SCCs; the identified genes not only inhibited cell cycle progression, but also promoted the malignant properties of SCCs. On the whole, the present study successfully identified SCCs in ES cells through a label-retaining system using CFSE. Moreover, to the best of our knowledge, the present study is the first to describe the characteristic properties of SCCs in ES. The findings of this study, if confirmed, may prove to be useful in elucidating the underlying molecular mechanisms and identifying effective therapeutic targets for ES.