Hypoxic Cancer Cells-Derived Exosomes Strengthen the Development of Cancer Stem Cell-Like Properties Through Delivering LINC00665 in Thyroid Cancer Cells.

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Ming Zhou, Chengcheng Peng, Qiong Zhang, Yanchu Tong
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Abstract

Hypoxia is a common phenomenon for solid tumors due to a lack of effective vascular system, and has been deemed as an important factor that drives the progression of thyroid cancer (TC) via altering the characteristics of tumor cells. The present study suggested that hypoxic TC cells enhanced cancer stem cell properties and progression of TC by delivering long intergenic non-protein coding RNA 665 (LINC00665)-containing exosomes. Specifically, TPC1 cells were exposed to normoxic or hypoxic environment, and it was found that hypoxic TPC1 cells-secreted exosomes (H-exo) were enriched with LINC00665, compared to normoxic TPC1 cells-derived exosomes (N-exo). In addition, by establishing the in vitro exosomes-TC cells coculture system, we found that in contrast to N-exo, H-exo apparently promoted cell proliferation, epithelial mesenchymal transition (EMT) and cancer stem cell properties via delivering LINC00665. This was supported by the in vivo results that H-exo transferred LINC00665 to promote tumorigenesis and the expression of EMT and stemness-associated markers in xenograft tumor-bearing mice models. Further mechanical experiments validated that LINC00665 combined with EPHB4 mRNA to sustain its stability to enhance cancer aggressiveness of TC. Altogether, our findings verified that hypoxic TC cells-secreted exosomes regulated the LINC00665/EPHB4 axis to enhance cancer stem cell properties of TC, providing novel signatures for TC diagnosis and therapy.

缺氧癌细胞来源的外泌体通过在甲状腺癌细胞中传递LINC00665加强癌症干细胞样特性的发展
由于缺乏有效的血管系统,缺氧是实体肿瘤的常见现象,并且被认为是通过改变肿瘤细胞的特性来驱动甲状腺癌(TC)进展的重要因素。目前的研究表明,缺氧TC细胞通过传递含有长基因间非蛋白编码RNA 665 (LINC00665)的外泌体,增强了癌症干细胞的特性和TC的进展。具体来说,将TPC1细胞暴露于常氧或缺氧环境中,发现与常氧TPC1细胞来源的外泌体(N-exo)相比,缺氧TPC1细胞分泌的外泌体(H-exo)富含LINC00665。此外,通过建立体外外泌体- tc细胞共培养系统,我们发现与N-exo相比,H-exo通过传递LINC00665明显促进细胞增殖、上皮间充质转化(epithelial mesenchymal transition, EMT)和肿瘤干细胞特性。H-exo转移LINC00665促进异种移植瘤小鼠模型的肿瘤发生以及EMT和干细胞相关标志物的表达,这一体内结果支持了这一点。进一步的力学实验证实,LINC00665与EPHB4 mRNA结合,维持其稳定性,增强TC的肿瘤侵袭性。总之,我们的研究结果证实了缺氧TC细胞分泌的外泌体调节LINC00665/EPHB4轴以增强TC的癌症干细胞特性,为TC的诊断和治疗提供了新的特征。
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来源期刊
Cell Biology International
Cell Biology International 生物-细胞生物学
CiteScore
7.60
自引率
0.00%
发文量
208
审稿时长
1 months
期刊介绍: Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
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索莱宝
penicillin/streptomycin solution
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fetal bovine serum (FBS)
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