Anti‑neuropilin‑1 monoclonal antibody suppresses the migration and invasion of human gastric cancer cells via Akt dephosphorylation

Abstract

Neuropilin-1 (NRP-1) is involved in a range of physiological and pathological processes, including neuronal cell guidance, cardiovascular development, immunity, angiogenesis and the pathogenesis of cancer. Targeting of NRP-1 is considered to be a potential cancer therapy and a number of approaches have been investigated, including the use of small interfering RNA, peptides, soluble NRP antagonists and monoclonal antibodies. The present study used a novel anti-neuropilin-1 monoclonal antibody (anti-NRP-1 mAb) to investigate its potential anti-tumor effects on human gastric cancer cells in vitro and in vivo, as well as its underlying mechanisms of action. Using an MTT assay, it was observed that anti-NRP-1 mAb (<150 µg/ml) had no effects on the viability of gastric cancer cell line BGC-823, while a Boyden chamber assay indicated that treatment with anti-NRP-1 mAb suppressed the migration and invasion of BGC-823 cells. Western blot analysis also demonstrated that phosphorylation of Akt was reduced in BGC-823 cells treated with anti-NRP-1 mAb. Furthermore, anti-NRP-1 mAb suppressed the growth of gastric cancer xenograft tumors and downregulated the expression of vascular endothelial growth factor proteins within tumors in nude mice. These data indicate the potential effects of anti-NRP-1 mAb on malignant tumors and suggest that inhibition of NRP-1 function with anti-NRP-1 mAb may be a novel therapeutic approach in the treatment of cancer.

[Retracted] Pancancer Analysis of Neurovascular‐Related NRP Family Genes as Potential Prognostic Biomarkers of Bladder Urothelial Carcinoma

“…This indicates that immunotherapy targeting NRP1 may have good clinical outcomes [42]. NRP1 has also been previously found to promote tumour angiogenesis, tumour proliferation, and migration [43][44][45][46][47][48]. Anti-NRP1 therapy can block tumour angiogenesis and upregulate the antitumour immune response [49][50][51][52].…”

Clinicopathological Significance of Neuropilin 1 Expression in Gastric Cancer: A Meta-Analysis

“…Published data have shown that the analysis of NRP1 expression levels could provide a predictive marker of clinical outcome and prognosis in gastric cancer [ 5 , 21 , 26 , 27 ]. Also, it is an exciting and challenging endeavor to employ NRP1-inhibitory strategies for cancer treatment [ 6 , 28 ]. Therefore, studies on the relationship of NRP1 expression and clinicopathological characteristics of GC by IHC emerged with inconclusive results from different publications.…”

“…In gastric cancer (GC), high expression of NRP1 is closely related to the development of tumor progression and associated with poor overall survival [ 5 ]. Furthermore, recent report indicated that anti-NRP-1 mAb might be a novel therapeutic approach in the treatment of gastric cancer [ 6 ].…”

Targeting neuropilin-1 interactions is a promising anti-tumor strategy

“…NRP1 promotes tumor cell growth, migration, invasion, and survival by interacting with several growth factors and their cognate signaling receptors. [ 92 – 96 ] Binding of VEGFA to NRP1 promotes RhoA activation and then, activated RhoA contributes to the degradation of p27kip1, which in turn, promotes tumor cell proliferation. This has been demonstrated in skin cancer, prostate cancer, and glioblastoma [ 60 , 97 – 99 ] [Figure 4 ].…”