论文标题
磁铁纳米接管有效捕获上皮和间质癌细胞
Magnetic Iron Nanocubes Effectively Capture Epithelial and Mesenchymal Cancer Cells
论文作者
论文摘要
捕获循环肿瘤细胞(CTC)的当前方法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,肿瘤细胞经历上皮到间质转化(EMT),可能导致CK/EPCAM表达的丧失。因此,至关重要的是开发独立于癌细胞上CK/EPCAM表达的捕获技术。为了开发这种技术,重要的是要在EMT之前和之后识别在肿瘤细胞上过表达的常见继发性致癌标记。我们分析了EMT之前和之后肿瘤细胞中的生物标志物表达水平,并发现了两个常见的蛋白质人表皮生长因子受体2(HER2)和表皮生长因子受体(EGFR),它们的水平不受影响。因此,我们合成了与HER2或EGFR的抗体共轭的免疫磁性铁纳米管,以捕获癌细胞,与EMT状态无关。纳米管在将感兴趣的细胞与血清中的细胞混合物中分离出来时显示出很高的特异性(6至9倍)。我们表征了捕获的细胞以识别其EMT状态。因此,我们认为此处介绍的结果将有助于制定新的策略,以捕获患者血液中原发性和转移性癌细胞以制定有效的治疗计划。
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.