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Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy

  • 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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Document Type:Article
Author:Diana B. PeckysORCiD, Daniel Gaa, Niels de JongeORCiD
Parent Title (English):Cell
First Page:3244
Year of first Publication:2021
Release Date:2022/09/23
Tag:EGFR; HER2; breast cancer; cancer cell heterogeneity; gastric cancer
Impact:07.666 (2021)
Funding Information:Deutsche Forschungsgemeinschaft (SFB1027-C7); Else Kröner-Fresenius-Stiftung
Groups:Innovative Elektronenmikroskopie
DDC classes:600 Technik, Medizin, angewandte Wissenschaften / 610 Medizin, Gesundheit
Open Access:Open Access
Signature:INM 2021/138
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International