In situ drug-receptor binding kinetics in single cells: a quantitative label-free study of anti-tumor drug resistance.
In situ drug-receptor binding kinetics in single cells: a quantitative label-free study of anti-tumor drug resistance.
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单细胞中的原位药物受体结合动力学：抗肿瘤耐药性的定量无标记研究
DOI：
10.1038/srep06609
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发表时间：
2014-10-14
影响因子：
4.6
通讯作者：
Tao N
中科院分区：
文献类型：
--
作者：
Wang W;Yin L;Gonzalez-Malerva L;Wang S;Yu X;Eaton S;Zhang S;Chen HY;LaBaer J;Tao N
Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situ Herceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.
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影响因子：
1.8
作者：
Darling, RJ;Brault, PA
通讯作者：
Brault, PA
影响因子：
15
作者：
Knezevic, Jelena;Langer, Andreas;Rant, Ulrich
通讯作者：
Rant, Ulrich
影响因子：
2.2
作者：
Xie, L;Jones, RM;Grace, MJ
通讯作者：
Grace, MJ
影响因子：
3.7
作者：
Kute, T;Lack, CM;Vaughn, JP
通讯作者：
Vaughn, JP
影响因子：
6.4
作者：
Price-Schiavi, SA;Jepson, S;Carraway, KL
通讯作者：
Carraway, KL