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.

Modeling Neoadjuvant chemotherapy resistance in vitro increased NRP‐1 and HER2 expression and converted MCF7 breast cancer subtype

“…This finding could be due to paclitaxel inhibiting the crosstalk between NRP‐1 and FAK (Ellison et al, ), leading to inhibition of the FAK pathway and NRP‐1 simultaneously. This would be consistent with earlier findings showing NRP‐1 inhibition suppressing the FAK/p130cas signalling pathway in MCF7 cells (Zeng et al, ). The integrin β3 levels in MCF7 cells resistant to 4xAC, were decreased, with a concurrent increase in NRP‐1 and p‐FAK, a correlation consistent with a previous report showing that integrin β3 suppression induced a neuropilin‐1‐dependent change in FAK remodelling (Ellison et al, ).…”

Neuropilin-1 is a host factor for SARS-CoV-2 infection

“…The interaction between S1 and NRP1 can be reduced by monoclonal antibodies that bind to the CendR-binding pocket of NRP1 b1. Disrupting CendR-peptide binding to neuropilins by antibodies and oligopeptide/peptidomimetics has been recognised as a potential anti-cancer strategy [18][19][20][21][22][23][24][25] , and the same approach may provide a route to COVID-19 therapies.…”

miR-376a inhibits breast cancer cell progression by targeting neuropilin-1 NR

“…We are not sure whether miR-376b holds similar effects to miR-376a, and whether miR-376a and miR-376b could exert additive effects on breast cancer progression, which should be evaluated in the future works. Based on the critical roles of NRP-1 in breast cancer progression, potential methods targeting NRP-1 were elucidated in several groups;10,11 however, the clinical application is still not shown, which might remind us that the mechanisms by which NRP-1 is regulated or NRP-1 functioned still need much more elucidations. In this work, we showed that miR-376a could regulate NRP-1 expression at the transcriptional level, and other miRNAs or other regulatory mechanisms by which NRP-1 was regulated at the translational level should be identified.…”

“…NRP-1 is an angiogenic co-receptor of VEGF-A, and VEGF-A/NRP-1 axis could promote breast cancer progression via enhancement of epithelial–mesenchymal transition (EMT) and activation of NF-κB and β-catenin signaling 8. Notably, a previous research has reported that peptides inhibiting the binding of VEGF-A/NRP-1 could inhibit breast cancer progression,9 and two groups have demonstrated that a monoclonal antibody targeting neuropilin-1 or a neuropilin-1 antagonist could exert anticancer effects in breast cancer via in vitro and in vivo experiments 10,11. Our studies have previously shown that RNA interference-mediated NRP-1 silencing could inhibit breast cancer cell proliferation and promote cell apoptosis, and VEGF-A/NRP-1 pathway could confer cancer stemness via activating Wnt/β-Catenin axis in breast cancer cells 12,13.…”