title: A monoclonal antibody targeting neuropilin-1 inhibits adhesion of MCF7 breast cancer cells to fibronectin by suppressing the FAK/p130cas signaling pathway.
abstract: 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-α5β1 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.
authors.affiliation: aCancer Research Center, Medical College bDepartment of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Xiamen University cDepartment of Oncology, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian Province, China.
authors.forename: Fanwei
authors.initials: F
authors.lastname: Zeng
authors.forename: Fanghong
authors.initials: F
authors.lastname: Luo
authors.forename: Sha
authors.initials: S
authors.lastname: Lv
authors.forename: Haipeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Chang
authors.initials: C
authors.lastname: Cao
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
authors.forename: Shengyu
authors.initials: S
authors.lastname: Wang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Xianjiang
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Dou
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Dai
authors.forename: Mingjun
authors.initials: M
authors.lastname: He
authors.forename: Yafei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lv
authors.forename: Jianghua
authors.initials: J
authors.lastname: Yan
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D039942:Neuropilin-1 / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D050719:Crk-Associated Substrate Protein; D005353:Fibronectins; D039942:Neuropilin-1; D051416:Focal Adhesion Protein-Tyrosine Kinases