Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy.
Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy.
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DOI：
10.3390/cells10113244
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发表时间：
2021-11-19
期刊：
影响因子：
6
通讯作者：
de Jonge N
中科院分区：
文献类型：
--
作者：
Peckys DB;Gaa D;de Jonge N
目前，乳腺癌患者根据激素受体和人表皮生长因子受体2（HER2）的表达水平进行唯一分类。这种粗略的分类不足以捕捉疾病的表型复杂性和异质性。开发了一种方法，用于绝对定量HER2及其家族成员（HER2过表达乳腺癌细胞质膜中的表皮生长因子受体（EGFR））的受体表面密度ρR、分子相互作用（二聚化）以及相关异质性。定量，相关光学显微镜（LM）和液相电子显微镜（LPEM）结合量子点（QD）标记。受体的单分子位置数据从完整癌细胞的扫描透射电子显微镜（STEM）图像获得。检测并统计分析了超过280，000个受体位置。一个重要的发现是亚细胞异质性异源二聚体份额相对于质膜区域具有不同的动态特性。推导单个癌细胞中EGFR和HER2 ρR及其二聚体百分比和异质性的定量信息，可能与早期识别HER2过表达肿瘤患者相关，这些肿瘤包含EGFR二聚体的比例增加，可能增加耐药性风险，因此需要额外的靶向治疗策略。
Currently, breast cancer patients are classified uniquely according to the expression level of hormone receptors, and human epidermal growth factor receptor 2 (HER2). This coarse classification is insufficient to capture the phenotypic complexity and heterogeneity of the disease. A methodology was developed for absolute quantification of receptor surface density ρR, and molecular interaction (dimerization), as well as the associated heterogeneities, of HER2 and its family member, the epidermal growth factor receptor (EGFR) in the plasma membrane of HER2 overexpressing breast cancer cells. Quantitative, correlative light microscopy (LM) and liquid-phase electron microscopy (LPEM) were combined with quantum dot (QD) labeling. Single-molecule position data of receptors were obtained from scanning transmission electron microscopy (STEM) images of intact cancer cells. Over 280,000 receptor positions were detected and statistically analyzed. An important finding was the subcellular heterogeneity in heterodimer shares with respect to plasma membrane regions with different dynamic properties. Deriving quantitative information about EGFR and HER2 ρR, as well as their dimer percentages, and the heterogeneities thereof, in single cancer cells, is potentially relevant for early identification of patients with HER2 overexpressing tumors comprising an enhanced share of EGFR dimers, likely increasing the risk for drug resistance, and thus requiring additional targeted therapeutic strategies.
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影响因子：
5.2
作者：
Buocikova V;Rios-Mondragon I;Pilalis E;Chatziioannou A;Miklikova S;Mego M;Pajuste K;Rucins M;Yamani NE;Longhin EM;Sobolev A;Freixanet M;Puntes V;Plotniece A;Dusinska M;Cimpan MR;Gabelova A;Smolkova B
通讯作者：
Smolkova B
影响因子：
45.3
作者：
DiGiovanna, MP;Stern, DF;Thor, AD
通讯作者：
Thor, AD
影响因子：
1.2
作者：
Blach, Patricia;Keskin, Sercan;de Jonge, Niels
通讯作者：
de Jonge, Niels
影响因子：
7.3
作者：
Fiala, Gina J.;Kaschek, Daniel;Schamel, Wolfgang W. A.
通讯作者：
Schamel, Wolfgang W. A.
影响因子：
16.6
作者：
Chung, Inhee;Reichelt, Mike;Shao, Lily;Akita, Robert W.;Koeppen, Hartmut;Rangell, Linda;Schaefer, Gabriele;Mellman, Ira;Sliwkowski, Mark X.
通讯作者：
Sliwkowski, Mark X.