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评估 CD44 和 CD133 作为结直肠癌的肿瘤干细胞标志物。

Evaluation of CD44 and CD133 as cancer stem cell markers for colorectal cancer.

机构信息

Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.

出版信息

Oncol Rep. 2012 Oct;28(4):1301-8. doi: 10.3892/or.2012.1951. Epub 2012 Aug 6.

DOI:10.3892/or.2012.1951
PMID:22895640
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3981033/
Abstract

Colorectal cancer (CRC) is a major cause of cancer-related mortality in the world. Recently, a number of studies have demonstrated that cancer stem cells (CSCs) present in colorectal cancer tissues, are responsible for resistance to conventional therapies. Therefore, effective recognition of CSCs is of great importance. In the present study, to explore the potential characterizations of CSCs by the expression of specific cell surface markers such as CD133 and CD44, we screened six CRC cell lines using western blotting, immunofluorescence and flow cytometry. SW620, one of the six cell lines analyzed, was sorted into four subpopulations by fluorescence activated cell sorting (FACS). The capability of colony formation, proliferation rate, apoptosis, drug resistance, as well as their migratory and invasion potential were detected. The results revealed that the combination of CD44 and CD133 correlates with the features of CSCs in SW620 cells. CD44 positive cells showed more robust colony formation, higher proliferation, less spontaneous apoptosis, a higher resistance to drug-induced cell death, and were enriched after drug treatment. Among CD44 positive SW620 cells, the CD133 negative subpopulation was more migratory and invasive, which means that CD44+CD133- correlates with most of features proposed for CSCs. Overall, the data presented herein showed that CRCs have a wide range of expression for CD44 and CD133; it is unlikely the CSCs can be characterized by any single marker or the same set of markers for all colon cancer cells. For SW620 cells, the CSCs are likely represented by the CD44+CD133- surface marker. This finding of CSC markers represented by one positive and one negative is in line with CSCs in other tumors, such as CD34+CD38- for acute myeloid leukemia; CD44+CD24- for breast and pancreatic tumors. The absence of surface molecule(s) on CSCs will make it even more difficult to track and target this group of minority cells.

摘要

结直肠癌(CRC)是世界上癌症相关死亡的主要原因。最近,许多研究表明,结直肠癌细胞中的癌症干细胞(CSC)是导致对传统疗法产生抗性的原因。因此,有效识别 CSC 非常重要。在本研究中,为了通过特定细胞表面标志物(如 CD133 和 CD44)的表达来探索 CSC 的潜在特征,我们使用 Western blot、免疫荧光和流式细胞术筛选了六种 CRC 细胞系。在分析的六种细胞系之一的 SW620 中,通过荧光激活细胞分选(FACS)将其分为四个亚群。检测了集落形成能力、增殖率、细胞凋亡、耐药性以及迁移和侵袭能力。结果表明,CD44 和 CD133 的组合与 SW620 细胞中 CSC 的特征相关。CD44 阳性细胞表现出更强的集落形成能力、更高的增殖率、更少的自发细胞凋亡、对药物诱导的细胞死亡更高的抗性,并且在药物处理后富集。在 CD44 阳性的 SW620 细胞中,CD133 阴性亚群具有更强的迁移和侵袭能力,这意味着 CD44+CD133-与大多数提出的 CSC 特征相关。总体而言,本文提供的数据表明 CRC 对 CD44 和 CD133 的表达具有广泛的范围;CSC 不太可能通过任何单个标志物或所有结肠癌细胞的相同标志物来特征化。对于 SW620 细胞,CSC 可能由 CD44+CD133-表面标志物表示。这种由一个阳性和一个阴性表示的 CSC 标志物的发现与其他肿瘤中的 CSC 一致,例如急性髓性白血病中的 CD34+CD38-;乳腺癌和胰腺癌中的 CD44+CD24-。CSC 上缺乏表面分子(s)将使追踪和靶向这组少数细胞变得更加困难。

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