Neuropilin-1 is a protein that in humans is encoded by the NRP1gene.[5][6][7] In humans, the neuropilin 1 gene is located at 10p11.22. This is one of two human neuropilins.
Research has shown that neuropilin 1 facilitates entry of SARS-CoV-2 into cells, making it a possible target for future antiviral drugs.[9][10]
Implication in cancer
Neuropilin 1 has been implicated in the vascularization and progression of cancers. NRP1 expression has been shown to be elevated in a number of human patient tumor samples, including brain, prostate, breast, colon, and lung cancers and NRP1 levels are positively correlated with metastasis.[11][12][13][14][15][16]
In prostate cancer NRP1 has been demonstrated to be an androgen-suppressed gene, upregulated during the adaptive response of prostate tumors to androgen-targeted therapies and a prognostic biomarker of clinical metastasis and lethal PCa.[11] In vitro and in vivo mouse studies have shown membrane bound NRP1 to be proangiogenic and that NRP1 promotes the vascularization of prostate tumors.[17]
Elevated NRP1 expression is also correlated with the invasiveness of non-small cell lung cancer both in vitro and in vivo.[16]
Target for cancer therapies
As a co-receptor for VEGF, NRP1 is a potential target for cancer therapies. A synthetic peptide, EG3287, was generated in 2005 and has been shown to block NRP1 activity.[18] EG3287 has been shown to induce apoptosis in tumor cells with elevated NRP1 expression.[18] A patent for EG3287 was filed in 2002 and approved in 2003.[19] As of 2015 there were no clinical trials ongoing or completed for EG3287 as a human cancer therapy.
Soluble NRP1 has the opposite effect of membrane bound NRP1 and has anti-VEGF activity. In vivo mouse studies have shown that injections of sNRP-1 inhibits progression of acute myeloid leukemia in mice.[20]
^Bachelder RE, Crago A, Chung J, Wendt MA, Shaw LM, Robinson G, et al. (August 2001). "Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells". Cancer Research. 61 (15): 5736–5740. PMID11479209.
Takahashi T, Nakamura F, Jin Z, Kalb RG, Strittmatter SM (October 1998). "Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors". Nature Neuroscience. 1 (6): 487–493. doi:10.1038/2203. PMID10196546. S2CID38320889.
Rossignol M, Beggs AH, Pierce EA, Klagsbrun M (May 1999). "Human neuropilin-1 and neuropilin-2 map to 10p12 and 2q34, respectively". Genomics. 57 (3): 459–460. doi:10.1006/geno.1999.5790. PMID10329017.
Rossignol M, Gagnon ML, Klagsbrun M (December 2000). "Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms". Genomics. 70 (2): 211–222. doi:10.1006/geno.2000.6381. PMID11112349.
Walter JW, North PE, Waner M, Mizeracki A, Blei F, Walker JW, et al. (March 2002). "Somatic mutation of vascular endothelial growth factor receptors in juvenile hemangioma". Genes, Chromosomes & Cancer. 33 (3): 295–303. doi:10.1002/gcc.10028. PMID11807987. S2CID33428561.