Different antiproliferative effects of matuzumab and cetuximab in A431 cells are associated with persistent activity of the MAPK pathway

• Published in: European journal of cancer (1990) Vol. 45; no. 7; pp. 1265 - 1273
• Main Authors: Meira, Debora Dummer, Nóbrega, Isabel, de Almeida, Vitor Hugo, Mororó, Jânio S, Cardoso, Alexander M, Silva, Ricardo L.A, Albano, Rodolpho M, Ferreira, Carlos Gil
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.05.2009; Elsevier
• Subjects: 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; 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
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2008.12.012

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.