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Journal of Cancer Research and Clinical Oncology

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Open Access 01-04-2017 | Original Article – Cancer Research

Influence of the HER receptor ligand system on sensitivity to cetuximab and trastuzumab in gastric cancer cell lines

Authors: Julia Kneissl, Anja Hartmann, Nicole Pfarr, Franziska Erlmeier, Thomas Lorber, Simone Keller, Gwen Zwingenberger, Wilko Weichert, Birgit Luber

Published in: Journal of Cancer Research and Clinical Oncology | Issue 4/2017

Abstract

Purpose

Gastric cancer remains a major health concern, and improvement of the therapeutic options is crucial. Treatment with targeted therapeutics such as the EGFR-targeting antibody cetuximab or the HER2-targeting antibody trastuzumab is either ineffective or moderately effective in this disease, respectively. In this study, we analysed the involvement of the HER receptor ligands amphiregulin (AREG), epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF) and transforming growth factor alpha (TGFα) in the responsiveness of gastric cancer cell lines to cetuximab and trastuzumab.

Methods

A panel of 11 gastric cancer cell lines was characterized for cetuximab and trastuzumab sensitivity, ligand secretion and expression and activation of the HER receptors using WST-1 cell proliferation assays, ELISAs and Western blot analyses. We further investigated the effects of an exogenous ligand application on the cetuximab and trastuzumab sensitivity.

Results

We found no correlation between TGFα secretion and the sensitivity to cetuximab or trastuzumab. For AREG, we confirmed previous results indicating that this ligand is a positive predictor of cetuximab sensitivity. Exogenous HB-EGF was effective in rescuing sensitive cell lines from inhibition of cell proliferation by both, cetuximab and trastuzumab.

Conclusions

Our data indicate that HB-EGF may be a useful marker for the prediction of trastuzumab sensitivity in gastric cancer.

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Title: Influence of the HER receptor ligand system on sensitivity to cetuximab and trastuzumab in gastric cancer cell lines
Authors: Julia Kneissl
Anja Hartmann
Nicole Pfarr
Franziska Erlmeier
Thomas Lorber
Simone Keller
Gwen Zwingenberger
Wilko Weichert
Birgit Luber
Publication date: 01-04-2017
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 4/2017
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-016-2308-z

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Influence of the HER receptor ligand system on sensitivity to cetuximab and trastuzumab in gastric cancer cell lines

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

Methods

Results

Conclusions

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