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 d...

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Autores principales:	Diana B. Peckys, Daniel Gaa, Niels de Jonge
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cancer cell heterogeneity breast cancer gastric cancer EGFR HER2 EGFR/HER2 heterodimers Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a6fbea5363344dcd8716f489028e0932
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spelling	oai:doaj.org-article:a6fbea5363344dcd8716f489028e09322021-11-25T17:13:13ZQuantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy10.3390/cells101132442073-4409https://doaj.org/article/a6fbea5363344dcd8716f489028e09322021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3244https://doaj.org/toc/2073-4409Currently, 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 <i>ρ</i><sub>R</sub>, 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 <i>ρ</i><sub>R</sub>, 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.Diana B. PeckysDaniel GaaNiels de JongeMDPI AGarticlecancer cell heterogeneitybreast cancergastric cancerEGFRHER2EGFR/HER2 heterodimersBiology (General)QH301-705.5ENCells, Vol 10, Iss 3244, p 3244 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer cell heterogeneity breast cancer gastric cancer EGFR HER2 EGFR/HER2 heterodimers Biology (General) QH301-705.5
spellingShingle	cancer cell heterogeneity breast cancer gastric cancer EGFR HER2 EGFR/HER2 heterodimers Biology (General) QH301-705.5 Diana B. Peckys Daniel Gaa Niels de Jonge Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy
description	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 <i>ρ</i><sub>R</sub>, 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 <i>ρ</i><sub>R</sub>, 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.
format	article
author	Diana B. Peckys Daniel Gaa Niels de Jonge
author_facet	Diana B. Peckys Daniel Gaa Niels de Jonge
author_sort	Diana B. Peckys
title	Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy
title_short	Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy
title_full	Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy
title_fullStr	Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy
title_full_unstemmed	Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy
title_sort	quantification of egfr-her2 heterodimers in her2-overexpressing breast cancer cells using liquid-phase electron microscopy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a6fbea5363344dcd8716f489028e0932
work_keys_str_mv	AT dianabpeckys quantificationofegfrher2heterodimersinher2overexpressingbreastcancercellsusingliquidphaseelectronmicroscopy AT danielgaa quantificationofegfrher2heterodimersinher2overexpressingbreastcancercellsusingliquidphaseelectronmicroscopy AT nielsdejonge quantificationofegfrher2heterodimersinher2overexpressingbreastcancercellsusingliquidphaseelectronmicroscopy
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Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy

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