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arXiv 2010.02129q-bio.CBq-bio.QM
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磁性铁纳米立方体有效捕获上皮和间质癌细胞

Magnetic Iron Nanocubes Effectively Capture Epithelial and Mesenchymal Cancer Cells

Dhananjay Suresh, Shreya Ghoshdastidar, Abilash Gangula, Soumavo Mukherjee, Anandhi Upendran, Raghuraman Kannan

摘要:

目前用于捕获循环肿瘤细胞(CTC)的方法是基于癌细胞上细胞角蛋白(CK)或上皮细胞粘附分子(EpCAM)的过表达。然而,在转移过程中,肿瘤细胞经历上皮间质转化(EMT),这可导致CK/EpCAM表达的丧失。因此,开发一种不依赖于癌细胞上CK/EpCAM表达的捕获技术至关重要。为了发展这项技术,重要的是要确定共同的第二致癌标记物过表达的肿瘤细胞EMT之前和之后。我们分析了EMT前后肿瘤细胞中生物标志物的表达水平,发现两种常见的蛋白质人表皮生长因子受体2(Her 2)和表皮生长因子受体(EGFR)的水平不受影响。因此,我们合成了与Her 2或EGFR抗体共价结合的免疫磁性铁纳米立方体,以捕获癌细胞,而不管EMT状态如何。纳米立方体在从血清中掺入的细胞混合物中分离感兴趣的癌细胞方面显示出高特异性(6至9倍)。我们表征了捕获的细胞以鉴定其EMT状态。因此,我们相信,这里提出的结果将有助于开发从患者血液中捕获原发性和转移性癌细胞的新策略,以制定有效的治疗计划。

英文摘要:

Current methods for capturing circulating tumor cells (CTCs) are based on the overexpression of cytokeratin (CK) or epithelial cell-adhesion molecule (EpCAM) on cancer cells. However, during the process of metastasis, tumor cells undergo epithelial to mesenchymal transition (EMT) that can lead to the loss of CK/EpCAM expression. Therefore, it is vital to develop a capturing technique independent of CK/EpCAM expression on the cancer cell. To develop this technique, it is important to identify common secondary oncogenic markers overexpressed on tumor cells before and after EMT. We analyzed the biomarker expression levels in tumor cells, before and after EMT, and found two common proteins human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) whose levels remained unaffected. So, we synthesized immunomagnetic iron nanocubes covalently conjugated with antibodies of Her2 or EGFR to capture cancer cells irrespective of the EMT status. The nanocubes showed high specificity (6 to 9 fold) in isolating the cancer cells of interest from a mixture of cells spiked in serum. We characterized the captured cells for identifying their EMT status. Thus, we believe the results presented here would help in the development of novel strategies for capturing both primary and metastatic cancer cells from patients blood to develop an effective treatment plan.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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