期刊
ANALYTICAL CHEMISTRY
卷 91, 期 13, 页码 8374-8382出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.9b01181
关键词
-
资金
- National Cancer Institute (NCI)/National Institutes of Health (NIH) [1R01-CA182528, 1R43-CA232924]
- National Science Foundation (NSF) [CBET-0931472]
- DRP program of the Wisconsin HNC SPORE Grant [P50-DE026787]
Detection of circulating tumor cells (CTCs) relying on their expression of epithelial cell markers, such as epithelial cell adhesion molecule (EpCAM), has been commonly used. However, this approach unlikely captures CTCs that have undergone the process of epithelial-mesenchymal transition (EMT). In this study, we have induced EMT of in vitro prostate (PCa) and breast cancer (BCa) cell lines by treatment of transforming growth factor beta(1) (TGF beta(1)) a pleiotropic cytokine with transition-regulating activities. We found that the TGF beta(1)-treated, post-EMT cells exhibited up to a 45% reduction in binding affinity to antibodies against EpCAM (aEpCAM). To overcome this limitation, we designed our capture platform that integrates a unique combination of biomimetic cell rolling, dendrimer-mediated multivalent binding, and antibody cocktails of aEpCAM/aEGFR/aHER-2. Our capture surfaces resulted in up to 98% capture efficiency of post-EMT cells from mixtures of TGF beta(1)-treated and untreated cancer cells spiked in culture media and human blood. In a clinical pilot study, our CTC device was also able to capture rare CTCs from PCa patients with significantly enhanced capture sensitivity and purity compared to the control surface with aEpCAM only, demonstrating its potential to provide a reliable detection solution for CTCs regardless of their EMT status.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据