Yoshifumi Matsumoto1, Hiroyuki Sakurai2, Yasunao Kogashiwa3, Toru Kimura2, Yuma Matsumoto1, Takashi Shionome4, Masatake Asano5, Koichiro Saito1, Naoyuki Kohno1. 1. Department of Otolaryngology, Head and Neck Surgery, Kyorin University School of Medicine, Tokyo, Japan. 2. Departments of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan. 3. Department of Head and Neck Surgery and Otolaryngology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan. 4. Department of Partial Denture Prosthodontics, Nihon University School of Dentistry, Kanda, Chiyoda-ku, Tokyo, Japan. 5. Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan, Kanda, Chiyoda-ku, Tokyo, Japan.
Abstract
BACKGROUND: Despite improved survival by the addition of a monoclonal antibody against epidermal growth factor receptor (EGFR), cetuximab, to chemotherapy or radiotherapy for squamous cell carcinoma of the head and neck (SCCHN), cetuximab by itself is not a potent antiproliferative agent against SCCHN. We aimed to elucidate working mechanism of cetuximab in SCCHN. METHODS: The effect of cetuximab on the proliferation, migration, invasion, epithelial-mesenchymal transition, and signaling events downstream of the EGFR were investigated in 4 SCCHN cell lines. The in vivo efficacy of cetuximab was evaluated in a xenotransplant model. RESULTS: Cetuximab inhibited migration, invasion, epithelial-mesenchymal transition, and lymph node metastasis by suppressing EGFR-GEP100-Arf6-AMAP1 pathway, but it did not inhibit cancer cell proliferation. CONCLUSION: The improved survival by the addition of cetuximab is likely to be attributable to the antiepithelial-mesenchymal transition action of cetuximab via inhibiting EGFR-GEP100-Arf6-AMAP1 pathway.
BACKGROUND: Despite improved survival by the addition of a monoclonal antibody against epidermal growth factor receptor (EGFR), cetuximab, to chemotherapy or radiotherapy for squamous cell carcinoma of the head and neck (SCCHN), cetuximab by itself is not a potent antiproliferative agent against SCCHN. We aimed to elucidate working mechanism of cetuximab in SCCHN. METHODS: The effect of cetuximab on the proliferation, migration, invasion, epithelial-mesenchymal transition, and signaling events downstream of the EGFR were investigated in 4 SCCHN cell lines. The in vivo efficacy of cetuximab was evaluated in a xenotransplant model. RESULTS:Cetuximab inhibited migration, invasion, epithelial-mesenchymal transition, and lymph node metastasis by suppressing EGFR-GEP100-Arf6-AMAP1 pathway, but it did not inhibit cancer cell proliferation. CONCLUSION: The improved survival by the addition of cetuximab is likely to be attributable to the antiepithelial-mesenchymal transition action of cetuximab via inhibiting EGFR-GEP100-Arf6-AMAP1 pathway.
Authors: Mathieu J F Crupi; Sarah M Maritan; Eduardo Reyes-Alvarez; Eric Y Lian; Brandy D Hyndman; Aisha N Rekab; Serisha Moodley; Costin N Antonescu; Lois M Mulligan Journal: Oncogene Date: 2019-10-23 Impact factor: 9.867
Authors: Laura C Zanetti-Domingues; Scott E Bonner; R Sumanth Iyer; Marisa L Martin-Fernandez; Veronica Huber Journal: Cells Date: 2020-12-08 Impact factor: 6.600