Matsumoto Yoshifumi, Sakurai Hiroyuki, Kogashiwa Yasunao, Kimura Toru, Matsumoto Yuma, Shionome Takashi, Asano Masatake, Saito Koichiro, Kohno Naoyuki
Department of Otolaryngology, Head and Neck Surgery, Kyorin University School of Medicine, Tokyo, Japan.
Departments of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Head Neck. 2017 Mar;39(3):476-485. doi: 10.1002/hed.24626. Epub 2016 Nov 23.
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.
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.
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.
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. © 2016 Wiley Periodicals, Inc. Head Neck 39: 476-485, 2017.
尽管对头颈部鳞状细胞癌（SCCHN）进行化疗或放疗时添加抗表皮生长因子受体（EGFR）单克隆抗体西妥昔单抗可提高生存率，但西妥昔单抗本身并非针对SCCHN的有效抗增殖剂。我们旨在阐明西妥昔单抗在SCCHN中的作用机制。
在4种SCCHN细胞系中研究了西妥昔单抗对增殖、迁移、侵袭、上皮-间质转化以及EGFR下游信号事件的影响。在异种移植模型中评估了西妥昔单抗的体内疗效。
西妥昔单抗通过抑制EGFR-GEP100-Arf6-AMAP1途径抑制迁移、侵袭、上皮-间质转化和淋巴结转移，但不抑制癌细胞增殖。
添加西妥昔单抗后生存率的提高可能归因于西妥昔单抗通过抑制EGFR-GEP100-Arf6-AMAP1途径的抗上皮-间质转化作用。©2016威利期刊公司。《头颈》39:476 - 485，2017。
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