Different antiproliferative effects of matuzumab and cetuximab in A431 cells are associated with persistent activity of the MAPK pathway
Abstract Preclinical studies have shown the potential antitumour efficacy of monoclonal antibodies (MAbs) directed to the epidermal growth factor receptor (EGFR). In this report, we investigated the cytotoxic effects of the MAb matuzumab (EMD 72000) towards A431 cells and compared it to cetuximab. W...
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Published in | European journal of cancer (1990) Vol. 45; no. 7; pp. 1265 - 1273 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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01.05.2009
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Abstract | Abstract Preclinical studies have shown the potential antitumour efficacy of monoclonal antibodies (MAbs) directed to the epidermal growth factor receptor (EGFR). In this report, we investigated the cytotoxic effects of the MAb matuzumab (EMD 72000) towards A431 cells and compared it to cetuximab. While cetuximab induced cell cycle arrest and inhibited A431 cell proliferation, matuzumab did not. Both MAbs inhibited growth factor induced EGFR, HER2 and AKT phosphorylation; however, only cetuximab inhibited ERK 1/2 phosphorylation. Taken together, the data indicate that each antibody may elicit different responses on EGFR downstream signalling pathways with a distinct impact on A431 cell line survival. When combined, MAbs synergistically inhibited cell proliferation and induced EGFR down-regulation with a strong inhibition of ERK1/2 and AKT phosphorylation. In addition, both MAbs efficiently inhibited VEGF expression and induced ADCC, highlighting their therapeutic potential in vivo when used either as a single agent or in combination. |
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AbstractList | Abstract Preclinical studies have shown the potential antitumour efficacy of monoclonal antibodies (MAbs) directed to the epidermal growth factor receptor (EGFR). In this report, we investigated the cytotoxic effects of the MAb matuzumab (EMD 72000) towards A431 cells and compared it to cetuximab. While cetuximab induced cell cycle arrest and inhibited A431 cell proliferation, matuzumab did not. Both MAbs inhibited growth factor induced EGFR, HER2 and AKT phosphorylation; however, only cetuximab inhibited ERK 1/2 phosphorylation. Taken together, the data indicate that each antibody may elicit different responses on EGFR downstream signalling pathways with a distinct impact on A431 cell line survival. When combined, MAbs synergistically inhibited cell proliferation and induced EGFR down-regulation with a strong inhibition of ERK1/2 and AKT phosphorylation. In addition, both MAbs efficiently inhibited VEGF expression and induced ADCC, highlighting their therapeutic potential in vivo when used either as a single agent or in combination. Preclinical studies have shown the potential antitumour efficacy of monoclonal antibodies (MAbs) directed to the epidermal growth factor receptor (EGFR). In this report, we investigated the cytotoxic effects of the MAb matuzumab (EMD 72000) towards A431 cells and compared it to cetuximab. While cetuximab induced cell cycle arrest and inhibited A431 cell proliferation, matuzumab did not. Both MAbs inhibited growth factor induced EGFR, HER2 and AKT phosphorylation; however, only cetuximab inhibited ERK 1/2 phosphorylation. Taken together, the data indicate that each antibody may elicit different responses on EGFR downstream signalling pathways with a distinct impact on A431 cell line survival. When combined, MAbs synergistically inhibited cell proliferation and induced EGFR down-regulation with a strong inhibition of ERK1/2 and AKT phosphorylation. In addition, both MAbs efficiently inhibited VEGF expression and induced ADCC, highlighting their therapeutic potential in vivo when used either as a single agent or in combination. |
Author | Meira, Debora Dummer de Almeida, Vitor Hugo Albano, Rodolpho M Mororó, Jânio S Nóbrega, Isabel Silva, Ricardo L.A Cardoso, Alexander M Ferreira, Carlos Gil |
Author_xml | – sequence: 1 fullname: Meira, Debora Dummer – sequence: 2 fullname: Nóbrega, Isabel – sequence: 3 fullname: de Almeida, Vitor Hugo – sequence: 4 fullname: Mororó, Jânio S – sequence: 5 fullname: Cardoso, Alexander M – sequence: 6 fullname: Silva, Ricardo L.A – sequence: 7 fullname: Albano, Rodolpho M – sequence: 8 fullname: Ferreira, Carlos Gil |
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Keywords | MAPK pathway Matuzumab Monoclonal antibodies anti-EGFR Cetuximab A431 cells Antineoplastic agent Enzyme Transferases Mitogen-activated protein kinase Monoclonal antibody Biological activity Epidermal growth factor receptor Cancerology Established cell line |
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Snippet | Abstract Preclinical studies have shown the potential antitumour efficacy of monoclonal antibodies (MAbs) directed to the epidermal growth factor receptor... Preclinical studies have shown the potential antitumour efficacy of monoclonal antibodies (MAbs) directed to the epidermal growth factor receptor (EGFR). In... |
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SubjectTerms | A431 cells Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal, Humanized Antineoplastic Agents - pharmacology Biological and medical sciences Blotting, Western Cell Line, Tumor - drug effects Cell Proliferation - drug effects Cetuximab Down-Regulation Drug Synergism Enzyme Inhibitors - pharmacology ErbB Receptors - antagonists & inhibitors ErbB Receptors - metabolism Flavonoids - pharmacology Hematology, Oncology and Palliative Medicine Humans MAP Kinase Signaling System - drug effects MAPK pathway Matuzumab Medical sciences Monoclonal antibodies anti-EGFR Pharmacology. Drug treatments Phosphorylation Protein Binding Tumors Vascular Endothelial Growth Factor A - metabolism |
Title | Different antiproliferative effects of matuzumab and cetuximab in A431 cells are associated with persistent activity of the MAPK pathway |
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