A monoclonal antibody targeting neuropilin-1 inhibits adhesion of MCF7 breast cancer cells to fibronectin by suppressing the FAK/p130cas signaling pathway

作者：Zeng Fanwei; Luo Fanghong; Lv Sha; Zhang Haipeng; Cao Chang; Chen Xiaoli; Wang Shengyu; Li Zhe; Wang Xianjiang; Dou Xiaofeng; Dai Yujuan; He Mingjun; Zhang Yafei; Lv Haiyan; Yan Jianghua^*; Chen Yuqiang

来源：Anti-Cancer Drugs, 2014, 25(6): 663-672.

DOI：10.1097/CAD.0000000000000091

• adhesion
• anti-NRP-1 mAb
• focal adhesion kinase
• neuropilin-1
• alpha 5 beta 1 integrin

Neuropilin-1 (NRP-1) is a nontyrosine kinase coreceptor for semaphorin 3A and the vascular endothelial growth factor involved in tumor angiogenesis, growth, and metastasis and is regarded as a promising target for cancer therapy. In the present study, we investigated the effects of an anti-NRP-1 monoclonal antibody (mAb) that we generated for MCF7 breast cancer cellular adhesion studies. MTT, colony formation, and adhesion assays showed that our anti-NRP-1 mAb dose-dependently inhibited MCF7 proliferation and fibronectin adhesion, leading to a rounded cellular morphology. Further, rhodamine phalloidin stain revealed that fibronectin-dependent formation of actin stress fibers was inhibited by anti-NRP-1 mAb. Immunoprecipitation and western blot showed that anti-NRP-1 mAb treatment inhibited the formation of NRP-1-alpha 5 beta 1 integrin complexes and suppressed the phosphorylation of focal adhesion kinase and p130cas in MCF7 cells. These findings contribute to further understanding the NRP-1 function in cell adhesion and tumor metastasis. Moreover, our anti-NRP-1 mAb is a prospective drug candidate for tumor treatment.

• 出版日期2014-7
• 单位厦门大学