ArticleScientific reports2019
Mathematical modeling of drug-induced receptor internalization in the HER2-positive SKBR3 breast cancer cell-line.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Measurement of specific and nonspecific tissue uptake of antibodies in tumor by SPECT imaging and nonlinear compartmental modeling.EJNMMI research · 2025Article
- Synthesis and Characterization of Multifunctional Fluorescent-Magnetic Platinum Nanoclusters.ACS omega · 2024Article
- EGFR-directed antibodies promote HER2 ADC internalization and efficacy.Cell reports. Medicine · 2024Article
- Targeted therapies in HER2-positive breast cancer with receptor-redirected Arazyme-linker-Herceptin as a novel fusion protein.Breast cancer (Tokyo, Japan) · 2024Article
- EGFR trafficking: effect of dimerization, dynamics, and mutation.Frontiers in oncology · 2023Review
- Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer.Cancers · 2022Article
- Anti-disialoganglioside antibody internalization by neuroblastoma cells as a mechanism of immunotherapy resistance.Cancer immunology, immunotherapy : CII · 2022Article
- Trastuzumab in combination with PEGylated interferon-α1b exerts synergistic antitumor activity through enhanced inhibition of HER2 downstream signaling and antibody-dependent cellular cytotoxicity.American journal of cancer research · 2022Article
- Bispecific antibodies with Fab-arms featuring exchanged antigen-binding constant domains.Biochemistry and biophysics reports · 2021Article
- Rate of Immune Complex Cycling in Follicular Dendritic Cells Determines the Extent of Protecting Antigen Integrity and Availability to Germinal Center B Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Novel SIRPα Antibodies That Induce Single-Agent Phagocytosis of Tumor Cells while Preserving T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Red-Fluorescent Pt Nanoclusters for Detecting and Imaging HER2 in Breast Cancer Cells.ACS omega · 2020Article
- Design and Synthesis of Megamolecule Mimics of a Therapeutic Antibody.Journal of the American Chemical Society · 2020Article
- Improving Receptor-Mediated Intracellular Access and Accumulation of Antibody Therapeutics-The Tale of HER2.Antibodies (Basel, Switzerland) · 2020Review
- Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models.Cancers · 2020Review
- Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
About 20% of breast cancer tumors over-express the HER2 receptor. Trastuzumab, an approved drug to treat this type of breast cancer, is a monoclonal antibody directly binding at the HER2 receptor and ultimately inhibiting cancer cell growth. The goal of our study was to understand the early impact of trastuzumab on HER2 internalization and recycling in the HER2-overexpressing breast cancer cell line SKBR3. To this end, fluorescence microscopy, monitoring the amount of HER2 expression in the plasma membrane, was combined with mathematical modeling to derive the flux of HER2 receptors from and to the membrane. We constructed a dynamic multi-compartment model based on ordinary differential equations. To account for cancer cell heterogeneity, a first, dynamic model was expanded to a second model including two distinct cell phenotypes, with implications for different conformational states of HER2, i.e. monomeric or homodimeric. Our mathematical model shows that the hypothesis of fast constitutive HER2 recycling back to the plasma membrane does not match the experimental data. It conclusively describes the experimental observation that trastuzumab induces sustained receptor internalization in cells with membrane ruffles. It is also concluded that for rare, non-ruffled (flat) cells, HER2 internalization occurs three orders of magnitude slower than for the bulk, ruffled cell population.
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