Please use this identifier to cite or link to this item: doi:10.22028/D291-35042
Title: Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy
Author(s): Peckys, Diana B.
Gaa, Daniel
de Jonge, Niels
Language: English
Title: Cells
Volume: 10
Issue: 11
Publisher/Platform: MDPI
Year of Publication: 2021
Free key words: cancer cell heterogeneity
breast cancer
gastric cancer
EGFR/HER2 heterodimers
correlative light- and liquid-phase electron microscopy
single molecule detection
absolute quantification
DDC notations: 500 Science
610 Medicine and health
Publikation type: Journal Article
Abstract: 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 interac tion (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.
DOI of the first publication: 10.3390/cells10113244
Link to this record: urn:nbn:de:bsz:291--ds-350422
ISSN: 2073-4409
Date of registration: 13-Dec-2021
Description of the related object: Supplementary Material
Related object:
Faculty: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Department: M - Biophysik
NT - Physik
Professorship: M - Keiner Professur zugeordnet
NT - Keiner Professur zugeordnet
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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