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用于识别循环乳腺肿瘤细胞的乳腺珠蛋白A和乳腺珠蛋白B适体的体外筛选。

In vitro selections of mammaglobin A and mammaglobin B aptamers for the recognition of circulating breast tumor cells.

作者信息

Hassan Eman M, Willmore William G, McKay Bruce C, DeRosa Maria C

机构信息

Institut national de la recherche scientifique - Energie, Materiaux Telecommunication 1650 boul. Lionel-Boulet, Varennes, Quebec, J3X1S2, Canada.

Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada.

出版信息

Sci Rep. 2017 Nov 3;7(1):14487. doi: 10.1038/s41598-017-13751-z.

DOI:10.1038/s41598-017-13751-z
PMID:29101327
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5670216/
Abstract

Mammaglobin B (MGB2) and mammaglobin A (MGB1) are proteins expressed in metastatic breast cancers. The early detection of circulating tumor cells (CTCs) in breast cancer patients is crucial to decrease mortality rate. Herein, novel aptamers were successfully selected and characterized against MGB2 and MGB1 proteins using a hybrid SELEX approach. The potential use of the selected aptamers in breast CTC detection was studied using spiked breast cancer cells in whole blood lysate. The results obtained from this study showed that the selected aptamers (MAMB1 and MAMA2) bind to their target breast cancer cell lines with high affinity (low nanomolar K values) and specificity. They also bind to their free recombinant target proteins and show minimal non-specific binding to normal and other cancer cell lines. Additionally, they were able to distinguish a low number of breast cancer cells spiked in whole blood lysate containing normal blood cells. The results obtained in this study indicate the great potential for the use of aptamers to detect MGB1 and MGB2 protein biomarkers, expressed on the surface of breast CTCs.

摘要

乳腺珠蛋白B(MGB2)和乳腺珠蛋白A(MGB1)是在转移性乳腺癌中表达的蛋白质。乳腺癌患者循环肿瘤细胞(CTC)的早期检测对于降低死亡率至关重要。在此,使用混合SELEX方法成功筛选并鉴定了针对MGB2和MGB1蛋白的新型适配体。使用全血裂解物中添加的乳腺癌细胞研究了所选适配体在乳腺CTC检测中的潜在用途。本研究获得的结果表明,所选适配体(MAMB1和MAMA2)以高亲和力(低纳摩尔K值)和特异性与其靶标乳腺癌细胞系结合。它们还与其游离的重组靶标蛋白结合,并且与正常和其他癌细胞系的非特异性结合最小。此外,它们能够区分添加到含有正常血细胞的全血裂解物中的少量乳腺癌细胞。本研究获得的结果表明,使用适配体检测乳腺CTC表面表达的MGB1和MGB2蛋白生物标志物具有巨大潜力。

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