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Tao, Qi; Spring, Simone C.; Terman, Bruce I.

doi:10.1023/a:1025884628155

Cited by 19 publications

(14 citation statements)

References 28 publications

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“…In addition to the membrane form, a naturally occurring soluble NRP-1 protein (sNRP-1), containing only part of the extracellular domain, is generated by alternative splicing of the NRP-1 gene (Figure 1 ) ( 31 , 32 ) and is thought to function as a natural inhibitor of the membrane NRP-1 by sequestering its ligands.…”

Section: Introductionmentioning

confidence: 99%

Neuropilin-1 as Therapeutic Target for Malignant Melanoma

Graziani

Lacal

2015

Front. Oncol.

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Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that acts as a co-receptor for various members of the vascular endothelial growth factor (VEGF) family. Its ability to bind or modulate the activity of a number of other extracellular ligands, such as class 3 semaphorins, TGF-β, HGF, FGF, and PDGF, has suggested the involvement of NRP-1 in a variety of physiological and pathological processes. Actually, this co-receptor has been implicated in axon guidance, angiogenesis, and immune responses. NRP-1 is also expressed in a variety of cancers (prostate, lung, pancreatic, or colon carcinoma, melanoma, astrocytoma, glioblastoma, and neuroblastoma), suggesting a critical role in tumor progression. Moreover, a growing amount of evidence indicates that NRP-1 might display important functions independently of other VEGF receptors. In particular, in the absence of VEGFR-1/2, NRP-1 promotes melanoma invasiveness, through the activation of selected integrins, by stimulating VEGF-A and metalloproteinases secretion and modulating specific signal transduction pathways. This review is focused on the role of NRP-1 in melanoma aggressiveness and on the evidence supporting its use as target of therapies for metastatic melanoma.

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Section: Introductionmentioning

confidence: 99%

Neuropilin-1 as Therapeutic Target for Malignant Melanoma

Graziani

Lacal

2015

Front. Oncol.

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“…The NRP1 and NRP2 genes are encoded at two different loci on chromosomes 10p12 and 2q34, respectively [21]. Due to RNA splicing, there are different membrane-bound and soluble splice variants of both NRPs; especially NRP2 comes in different variants, NRP2A and NRP2B (Figure 1) [22,23,24,25,26]. This diversity is further enhanced by optional insertion of 5, 17, or 22 amino acids C-terminal to amino acid 808 in the membrane-proximal part of the NRP ectodomain.…”

Section: Molecular Structure Of Nrpsmentioning

confidence: 99%

Neuropilins in the Context of Tumor Vasculature

Niland

Eble

2019

IJMS

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Neuropilin-1 and Neuropilin-2 form a small family of plasma membrane spanning receptors originally identified by the binding of semaphorin and vascular endothelial growth factor. Having no cytosolic protein kinase domain, they function predominantly as co-receptors of other receptors for various ligands. As such, they critically modulate the signaling of various receptor tyrosine kinases, integrins, and other molecules involved in the regulation of physiological and pathological angiogenic processes. This review highlights the diverse neuropilin ligands and interacting partners on endothelial cells, which are relevant in the context of the tumor vasculature and the tumor microenvironment. In addition to tumor cells, the latter contains cancer-associated fibroblasts, immune cells, and endothelial cells. Based on the prevalent neuropilin-mediated interactions, the suitability of various neuropilin-targeted substances for influencing tumor angiogenesis as a possible building block of a tumor therapy is discussed.

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“…Both s III NRP and s IV NRP have been shown to be expressed in normal and cancerous tissues and are capable of binding VEGF-A 165 , indicating that these two isoforms are antagonists for NRP1-mediated cellular activities [134]. The final isoform of NRP1 is NRP∆E16, which results from the skipping of exon 16 and replacement with an “AAG” Arg triple; however, this isoform does not have a functional difference to full length NRP1 [135].…”

Section: Vegfr Signaling Complexesmentioning

confidence: 99%

Modulation of Receptor Tyrosine Kinase Activity through Alternative Splicing of Ligands and Receptors in the VEGF-A/VEGFR Axis

Stevens

Oltean

2019

Cells

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Vascular endothelial growth factor A (VEGF-A) signaling is essential for physiological and pathological angiogenesis. Alternative splicing of the VEGF-A pre-mRNA gives rise to a pro-angiogenic family of isoforms with a differing number of amino acids (VEGF-Axxxa), as well as a family of isoforms with anti-angiogenic properties (VEGF-Axxxb). The biological functions of VEGF-A proteins are mediated by a family of cognate protein tyrosine kinase receptors, known as the VEGF receptors (VEGFRs). VEGF-A binds to both VEGFR-1, largely suggested to function as a decoy receptor, and VEGFR-2, the predominant signaling receptor. Both VEGFR-1 and VEGFR-2 can also be alternatively spliced to generate soluble isoforms (sVEGFR-1/sVEGFR-2). The disruption of the splicing of just one of these genes can result in changes to the entire VEGF-A/VEGFR signaling axis, such as the increase in VEGF-A165a relative to VEGF-A165b resulting in increased VEGFR-2 signaling and aberrant angiogenesis in cancer. Research into this signaling axis has recently focused on manipulating the splicing of these genes as a potential therapeutic avenue in disease. Therefore, further research into understanding the mechanisms by which the splicing of VEGF-A/VEGFR-1/VEGFR-2 is regulated will help in the development of drugs aimed at manipulating splicing or inhibiting specific splice isoforms in a therapeutic manner.

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Untitled

Cited by 19 publications

References 28 publications

Neuropilin-1 as Therapeutic Target for Malignant Melanoma

Neuropilin-1 as Therapeutic Target for Malignant Melanoma

Neuropilins in the Context of Tumor Vasculature

Modulation of Receptor Tyrosine Kinase Activity through Alternative Splicing of Ligands and Receptors in the VEGF-A/VEGFR Axis

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