Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells
Development of an ErbB4 monoclonal antibody that blocks neuregulin-1-induced ErbB4 activation in cancer cells
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开发一种 ErbB4 单克隆抗体，可阻断癌细胞中纽兰格林-1 诱导的 ErbB4 激活
DOI：
10.1016/j.bbrc.2016.01.045
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发表时间：
2016
影响因子：
3.1
通讯作者：
Nagano Osamu
中科院分区：
文献类型：
--
作者：
Okazaki Shogo;Nakatani Fumi;Masuko Kazue;Tsuchihashi Kenji;Ueda Shiho;Masuko Takashi;Saya Hideyuki;Nagano Osamu
使用单克隆抗体（mAb）进行癌症治疗是当前癌症治疗的最重要策略之一。受体酪氨酸激酶的表皮生长因子受体（EGFR）家族调节癌细胞增殖、存活和迁移，是基于抗体的治疗的主要分子靶标。ErbB 4/HER 4含有配体结合胞外区，可被几种配体激活，包括神经调节蛋白（NRG）、肝素结合EGF样生长因子、β细胞素和表皮调节蛋白。尽管临床上已经批准了ErbB 1和ErbB 2的抗体，但还没有ErbB 4的治疗性mAb，并且还不知道ErbB 4是否是基于抗体的癌症治疗的有用靶标。在这项研究中，我们开发了一种抗ErbB 4单克隆抗体（克隆P6-1），抑制NRG依赖性激活ErbB 4，并检查其对乳腺癌细胞增殖的影响，在细胞外基质。
The use of monoclonal antibodies (mAbs) for cancer therapy is one of the most important strategies for current cancer treatment. The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, which regulates cancer cell proliferation, survival, and migration, is a major molecular target for antibody-based therapy. ErbB4/HER4, which contains a ligand-binding extracellular region, is activated by several ligands, including neuregulins (NRGs), heparin-binding EGF-like growth factor, betacellulin and epiregulin. Although there are clinically approved antibodies for ErbB1 and ErbB2, there are no available therapeutic mAbs for ErbB4, and it is not known whether ErbB4 is a useful target for antibody-based cancer therapy. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix.