title: Gene status of head and neck squamous cell carcinoma cell lines and cetuximab-mediated biological activities.
abstract: Cetuximab is a chimeric IgG1 monoclonal antibody that targets epidermal growth factor receptor (EGFR). Cetuximab binds to EGFR and prevents phosphorylation of EGFR. Moreover, preclinical results have shown the ability of cetuximab to induce either complement-mediated tumor cell killing (CDC) or antibody-dependent cell-mediated-cytotoxicity (ADCC). We previously reported mutation in EGFR regarding head and neck squamous cell carcinoma (HNSCC) cell lines. In the present study, we analyzed the same 16 HNSCC cell lines for mutations in KRAS, PIK3CA, BRAF and PTEN. Furthermore, we evaluated cetuximab-mediated biological activities (antiproliferative effect by the MTT assay and ADCC) regarding these cell lines. Mutations in PIK3CA and PTEN were observed in two cell lines (2/16, 12.5%), but no mutation was observed in KRAS and BRAF. The antiproliferative effect of cetuximab by the MTT assay was not strong, and no correlation was observed between the antiproliferative effect of cetuximab and mutations in EGFR, KRAS, PIK3CA, BRAF and PTEN in these cell lines. Therefore, the mutation status of EGFR and downstream molecules were not useful for predicting the antitumor effects of cetuximab on HNSCC. Cetuximab-mediated ADCC was observed in these cell lines and might have been influenced by the expression of EGFR. Therefore, cetuximab-mediated ADCC seems to be an important part of the antitumor mechanisms of cetuximab and the expression levels of EGFR might influence the antitumor activity of cetuximab. Therefore, besides the antiproliferative effect of cetuximab by the MTT assay, it appeared important to evaluate cetuximab-mediated ADCC as well as EGFR expression in HNSCC cells.
authors.affiliation: Department of Biology and Function in Head and Neck, Yokohama City University Graduate School of Medicine, Yokohama, Japan. kondonorio@cick.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Kondo
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tsukuda
authors.forename: Takahide
authors.initials: T
authors.lastname: Taguchi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Nakazaki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sakakibara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Gabor
authors.initials: G
authors.lastname: Toth
authors.forename: Goshi
authors.initials: G
authors.lastname: Nishimura
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics*; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000068818:Cetuximab; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D011905:Genes, ras; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D009154:Mutation; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000068818:Cetuximab