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CD24、CD44 和 EpCAM 在外周血循环肿瘤细胞中富集用于建立新的鼻咽癌患者来源异种移植模型。

CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma.

机构信息

Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, 50588, Kuala, Lumpur, Malaysia.

Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603, Kuala, Lumpur, Malaysia.

出版信息

Sci Rep. 2017 Sep 28;7(1):12372. doi: 10.1038/s41598-017-12045-8.

Abstract

Subpopulations of nasopharyngeal carcinoma (NPC) contain cells with differential tumourigenic properties. Our study evaluates the tumourigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in NPC. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumourigenic cells leading to tumours with larger volume and higher mitotic figures. Although CD44br and EpCAMbr cells significantly enriched for tumour-initiating cells (TICs), all cells could retain self-renewal property for at least four generations. Compared to CD44 marker alone, EpCAM/CD44dbr marker did not enhance for cells with faster-growing ability or higher TIC frequency. Cells expressing high CD44 or EpCAM had lower KLF4 and p21 in NPC subpopulations. KLF4-overexpressed EpCAMbr cells had slower growth while Kenpaullone inhibition of KLF4 transcription increased in vitro cell proliferation. Compared to non-NPC, NPC specimens had increased expression of EPCAM, of which tumours from advanced stage of NPC had higher expression. Together, our study provides evidence that EpCAM is a potentially important marker in NPC.

摘要

鼻咽癌(NPC)的亚群包含具有不同肿瘤发生特性的细胞。我们的研究评估了 CD24、CD44、EpCAM 以及 EpCAM/CD44 细胞组合在 NPC 中的肿瘤发生潜能。CD44br 和 EpCAMbr 细胞富集了更高的 S 期细胞含量,生长更快的肿瘤起始细胞导致肿瘤体积更大和有更高的有丝分裂数。尽管 CD44br 和 EpCAMbr 细胞显著富集了肿瘤起始细胞(TICs),但所有细胞至少可以保持自我更新能力四代。与单独的 CD44 标志物相比,EpCAM/CD44dbr 标志物并没有增强具有更快生长能力或更高 TIC 频率的细胞。在 NPC 亚群中,高表达 CD44 或 EpCAM 的细胞中 KLF4 和 p21 的表达水平较低。过表达 KLF4 的 EpCAMbr 细胞生长较慢,而 Kenpaullone 抑制 KLF4 转录则增加了体外细胞增殖。与非 NPC 相比,NPC 标本中 EpCAM 的表达增加,其中 NPC 晚期肿瘤的表达更高。综上所述,我们的研究提供了证据表明 EpCAM 是 NPC 中一个潜在的重要标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc6/5620042/285d35a7ce89/41598_2017_12045_Fig1_HTML.jpg

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