Disease relevance of NRP2

• The level of npn2 mRNA in the retina increased during retinal vascular development, after exposure to hyperoxia, and after the onset of retinal ischemia [1].
• The osteosarcomas with NRP2 expression (n=24) showed a significantly increased vascularity (P<0.0014, Mann-Whitney U test) [2].
• Similar effects, but through NRP2, were observed in the C100 breast cancer cell line [3].
• We found that lung cancers (n = 34) always express the neuropilin-1 receptor for secreted semaphorins, whereas 82% expressed the neuropilin-2 receptor [4].
• NP-2 expression was not detected in neuroendocrine cells outside the gastroenteropancreatic system, or in their corresponding neoplasms, except for focal staining in one bronchial carcinoid tumour [5].

High impact information on NRP2

• Consistent with semaphorin-mediated chemorepulsion of neurons, tumor cells expressing SEMA3F were chemorepulsive for vascular and lymphatic endothelial cells expressing neuropilin-2 (NRP2), a novel mechanism for a tumor angiogenesis inhibitor [6].
• The repulsive activity was abrogated by NRP2 RNA interference [6].
• Lastly, neuropilin-1 can homomultimerize and form heteromultimers with neuropilin-2 [7].
• NRP2 specifically binds VEGF-A and VEGF-C, although the biological relevance of these interactions in human endothelial cells is poorly understood [8].
• Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cell survival and migration [8].

Biological context of NRP2

• Overexpression of NRP2 in primary human endothelial cells promoted cell survival induced by VEGF-A and VEGF-C [8].
• We find that expression of npn2 is downregulated in isl1-cre;smo mutants, suggesting an isl1/Shh/npn pathway required to affect morphogenesis at the anterior pole of the heart [9].
• Other factors that seem to be involved in lymphangiogenesis include the Tie/angiopoietin system, neuropilin-2 and integrin alpha 9 [10].
• Semaphorin 3F stimulates growth cone collapse following binding to the closest relative to neuropilin-1 in the genome, neuropilin-2 [11].
• Eighteen positive cDNA clones were isolated by TxCAD sera; DNA sequence analysis and DNA database searching identified all but one clone; 16 were nuclear or cytoplasmic proteins and 1 of them was the cell surface protein neuropilin 2 [12].

Anatomical context of NRP2

• Moreover, a siRNA targeting specifically NRP2 was a potent inhibitor of human endothelial cell migration induced by VEGF-A and VEGF-C [8].
• In this study, we investigated the expression of npn2 mRNA during new blood vessel growth in the retina and used npn2 knockout mice to assess the impact of deficiency of Npn2 on retinal NV [1].
• The function of NP-2 in islet cell biology or tumourigenesis remains to be elucidated [5].
• NP-2 expression has been recently localized to a subset of neuroendocrine cells in the gastrointestinal tract [5].
• Paraffin-embedded tissue sections from 30 endocrine pancreatic tumours (EPTs) and from normal pancreas were immunostained with a rabbit polyclonal antibody generated towards NP-2 [5].

Associations of NRP2 with chemical compounds

• Both np-2 forms bind VEGF(165) with high affinity in the presence of heparin (K(D) 1.3 x 10(-10) m) but not VEGF(121). np-2 also binds the heparin-binding form of placenta growth factor [13].
• The interaction of Neuropilin-1 and Neuropilin-2 with tyrosine-kinase receptors for VEGF [14].
• In the colon, the np-2-expressing subpopulation of neuroendocrine cell is almost identical with the serotonin-producing subpopulation of neuroendocrine cells [15].
• In the high-spin form of NP2, the proximal histidine plane is shown to be oriented 135 degrees clockwise from the heme N(II)-Fe-N(IV) axis, again for the B heme orientation [16].
• Methotrexate (MTX) was conjugated to an anti-carcinoembryonic antigen monoclonal antibody (NP2) by using amino-dextran as an intermediate carrier [17].

Other interactions of NRP2

• RESULTS: Eleven of 15 extraneoplastic specimens showed NRP1 expression (73.3%) and 8 showed NRP2 expression (53.3%) [18].
• Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity [7].
• Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected] [13].
• For VEGFR-1, VEGFR-2, NP-1, and NP-2, one major band was observed at 180, 235, 130, and 130 kDa, respectively [19].

Analytical, diagnostic and therapeutic context of NRP2

• Double in situ hybridization reveals that six-somite embryos contain intermingled extraembryonic blood island (BI) subpopulations that express np1 or np2 as well as a BI subpopulation that coexpresses both neuropilins [20].
• The human gene encoding PTP-NP-2 was assigned to human chromosome 7q22-qter using Southern blot analysis of genomic DNAs from rodent/human somatic hybrid cell lines [21].
• Northern blot analysis using cDNAs as probes indicated that mRNAs for both NP1 and NP2 occurred not in primary spermatocytes but in round spermatids [22].
• RT-PCR of the salivary glands showed that injections of 15mug of NP2 dsRNA in fourth-instar nymphs reduced gene expression by 75+/-14% and that feeding 1mug/muL of NP2 dsRNA into second-instar nymphs (approx. 13mug in total) reduced gene expression by 42+/-10% [23].

References