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Neuropilin structure governs VEGF and semaphorin binding and regulates angiogenesis

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Abstract

Neuropilins (NRP) play a central role in neuronal and blood vessel development as receptors for two ligand types, the semaphorin (SEMA) family of axon guidance modulators and the VEGF family of angiogenesis stimulators. The role of NRPs in axon guidance is well documented but a role in blood vessel development is less so. NRPs mediate normal developmental angiogenesis as shown in mouse and zebrafish models, and pathological angiogenesis in tumors and retinal disease. The ability of two disparate ligand families to bind to the same receptor is unusual but may be explainable by analysis of neuropilin structure. There are two NRP genes, nrp1 and nrp2. The NRPs have a relatively large extracellular domain consisting of sub domains, which are ligand binding sites. VEGF165 binds to the b1b2 subdomain, SEMA3A and SEMA3F also bind to b1b2 but to a1a2 as well. Mutagenesis studies have identified NRP amino acids that bind VEGF165 but not SEMA3F. These NRP structural elements might dictate differential SEMA and VEGF165 binding properties, which in turn regulate angiogenesis. This article reviews the latest information of NRP structure and how structure influences angiogenesis. In addition, the role of NRPs in human cancer is addressed.

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Abbreviations

NRP:

Neuropilin

SEMA:

Semaphorin

VEGF:

Vascular endothelial growth factor

VEGFR:

VEGF receptor

EC:

Endothelial cell

ISV:

Intersegmental vessels

References

  1. Fujisawa H et al (1997) Roles of a neuronal cell-surface molecule, neuropilin, in nerve fiber fasciculation and guidance. Cell Tissue Res 290(2):465–470

    Article  PubMed  CAS  Google Scholar 

  2. Klagsbrun M, Takashima S, Mamluk R (2002) The role of neuropilin in vascular and tumor biology. Adv Exp Med Biol 515:33–48

    PubMed  CAS  Google Scholar 

  3. Fujisawa H (2004) Discovery of semaphorin receptors, neuropilin and plexin, and their functions in neural development. J Neurobiol 59(1):24–33

    Article  PubMed  CAS  Google Scholar 

  4. Eichmann A, Makinen T, Alitalo K (2005) Neural guidance molecules regulate vascular remodeling and vessel navigation. Genes Dev 19(9):1013–1021

    Article  PubMed  CAS  Google Scholar 

  5. Klagsbrun M, Eichmann A (2005) A role for axon guidance receptors and ligands in blood vessel development and tumor angiogenesis. Cytokine Growth Factor Rev 16(4–5):535–548

    Article  PubMed  CAS  Google Scholar 

  6. Takagi S et al (1987) Specific cell surface labels in the visual centers of Xenopus laevis tadpole identified using monoclonal antibodies. Dev Biol 122(1):90–100

    Article  PubMed  CAS  Google Scholar 

  7. Takagi S et al (1991) The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors. Neuron 7(2):295–307

    Article  PubMed  CAS  Google Scholar 

  8. Kolodkin AL et al (1997) Neuropilin is a semaphorin III receptor. Cell 90(4):753–762

    Article  PubMed  CAS  Google Scholar 

  9. Chen H et al (1997) Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron 19(3):547–559

    Article  PubMed  CAS  Google Scholar 

  10. He Z, Tessier-Lavigne M (1997) Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90(4):739–751

    Article  PubMed  CAS  Google Scholar 

  11. Soker S et al (1998) Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92(6):735–745

    Article  PubMed  CAS  Google Scholar 

  12. Bielenberg DR, Klagsbrun M (2007) Targeting endothelial and tumor cells with semaphorins. Cancer Metastasis Rev 26(3–4):421–431

    Article  PubMed  CAS  Google Scholar 

  13. Ellis LM (2006) The role of neuropilins in cancer. Mol Cancer Ther 5(5):1099–1107

    Article  PubMed  CAS  Google Scholar 

  14. Geretti E, Klagsbrun M (2007) Neuropilins, novel targets for anti-angiogenesis therapies. Cell Adhes Migr 1(2):56–61

    Google Scholar 

  15. Pan Q et al (2007) Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell 11(1):53–67

    Article  PubMed  CAS  Google Scholar 

  16. Rosenfeld PJ et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355(14):1419–1431

    Article  PubMed  CAS  Google Scholar 

  17. Giger RJ et al (1998) Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity. Neuron 21(5):1079–1092

    Article  PubMed  CAS  Google Scholar 

  18. Nakamura F, Goshima Y (2002) Structural and functional relation of neuropilins. Adv Exp Med Biol 515:55–69

    PubMed  CAS  Google Scholar 

  19. Nakamura F et al (1998) Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse. Neuron 21(5):1093–1100

    Article  PubMed  CAS  Google Scholar 

  20. Renzi MJ et al (1999) A dominant negative receptor for specific secreted semaphorins is generated by deleting an extracellular domain from neuropilin-1. J Neurosci 19(18):7870–7880

    PubMed  CAS  Google Scholar 

  21. Roth L et al (2007) Transmembrane domain interactions control biological functions neuropilin-1. Mol Biol Cell 19(2):646–654

    Article  PubMed  CAS  Google Scholar 

  22. Rossignol M, Gagnon ML, Klagsbrun M (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

    Article  PubMed  CAS  Google Scholar 

  23. Cackowski FC et al (2004) Identification of two novel alternatively spliced Neuropilin-1 isoforms. Genomics 84(1):82–94

    Article  PubMed  CAS  Google Scholar 

  24. Gagnon ML et al (2000) Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: in vivo expression and antitumor activity. Proc Natl Acad Sci USA 97(6):2573–2578

    Article  PubMed  CAS  Google Scholar 

  25. Gluzman-Poltorak Z et al (2000) Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165. J Biol Chem 275(24):18040–18045

    Article  PubMed  CAS  Google Scholar 

  26. Gu C et al (2002) Characterization of neuropilin-1 structural features that confer binding to semaphorin 3A and vascular endothelial growth factor 165. J Biol Chem 277(20):18069–18076

    Article  PubMed  CAS  Google Scholar 

  27. Karpanen T et al (2006) Functional interaction of VEGF-C and VEGF-D with neuropilin receptors. Faseb J 20(9):1462–1472

    Article  PubMed  CAS  Google Scholar 

  28. Makinen T et al (1999) Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. J Biol Chem 274(30):21217–21222

    Article  PubMed  CAS  Google Scholar 

  29. Wise LM et al (2003) Viral vascular endothelial growth factors vary extensively in amino acid sequence, receptor-binding specificities, and the ability to induce vascular permeability yet are uniformly active mitogens. J Biol Chem 278(39):38004–38014

    Article  PubMed  CAS  Google Scholar 

  30. Sulpice E et al (2008) Neuropilin-1 and neuropilin-2 act as coreceptors, potentiating proangiogenic activity. Blood 111(4):2036–2045

    Article  PubMed  CAS  Google Scholar 

  31. West DC et al (2005) Interactions of multiple heparin binding growth factors with neuropilin-1 and potentiation of the activity of fibroblast growth factor-2. J Biol Chem 280(14):13457–13464

    Article  PubMed  CAS  Google Scholar 

  32. Geretti E et al (2007) Site-directed mutagenesis in the B-neuropilin-2 domain selectively enhances its affinity to VEGF165, but not to semaphorin 3F. J Biol Chem 282(35):25698–25707

    Article  PubMed  CAS  Google Scholar 

  33. Mamluk R et al (2002) Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain. J Biol Chem 277(27):24818–24825

    Article  PubMed  CAS  Google Scholar 

  34. Vander Kooi CW et al (2007) Structural basis for ligand and heparin binding to neuropilin B domains. Proc Natl Acad Sci USA 104(15):6152–6157

    Article  PubMed  CAS  Google Scholar 

  35. Miao HQ et al (1999) Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol 146(1):233–242

    Article  PubMed  CAS  Google Scholar 

  36. Appleton BA et al (2007) Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding. Embo J 26(23):4902–4912

    Article  PubMed  CAS  Google Scholar 

  37. Lee CC et al (2003) Crystal structure of the human neuropilin-1 b1 domain. Structure 11(1):99–108

    Article  PubMed  CAS  Google Scholar 

  38. Gu C et al (2003) Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development. Dev Cell 5(1):45–57

    Article  PubMed  CAS  Google Scholar 

  39. von Wronski MA et al (2006) Tuftsin binds neuropilin-1 through a sequence similar to that encoded by exon 8 of vascular endothelial growth factor. J Biol Chem 281(9):5702–5710

    Article  CAS  Google Scholar 

  40. Soker S et al (1996) Characterization of novel vascular endothelial growth factor (VEGF) receptors on tumor cells that bind VEGF165 via its exon 7-encoded domain. J Biol Chem 271(10):5761–5767

    Article  PubMed  CAS  Google Scholar 

  41. Soker S et al (1997) Inhibition of vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation by a peptide corresponding to the exon 7-encoded domain of VEGF165. J Biol Chem 272(50):31582–31588

    Article  PubMed  CAS  Google Scholar 

  42. Pan Q et al (2007) Neuropilin-1 binds to VEGF121 and regulates endothelial cell migration and sprouting. J Biol Chem 282(33):24049–24056

    Article  PubMed  CAS  Google Scholar 

  43. Shraga-Heled N et al (2007) Neuropilin-1 and neuropilin-2 enhance VEGF121 stimulated signal transduction by the VEGFR-2 receptor. Faseb J 21(3):915–926

    Article  PubMed  CAS  Google Scholar 

  44. Bates DO et al (2002) VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. Cancer Res 62(14):4123–4131

    PubMed  CAS  Google Scholar 

  45. Cebe Suarez S et al (2006) A VEGF-A splice variant defective for heparan sulfate and neuropilin-1 binding shows attenuated signaling through VEGFR-2. Cell Mol Life Sci 63(17):2067–2077

    Article  PubMed  CAS  Google Scholar 

  46. Bachelder RE et al (2001) Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells. Cancer Res 61(15):5736–5740

    PubMed  CAS  Google Scholar 

  47. Bachelder RE, Wendt MA, Mercurio AM (2002) Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4. Cancer Res 62(24):7203–7206

    PubMed  CAS  Google Scholar 

  48. Hu B. et al (2007) Neuropilin-1 promotes human glioma progression through potentiating the activity of the HGF/SF autocrine pathway. Oncogene 26(38):5577–5586

    Article  PubMed  CAS  Google Scholar 

  49. Wang L et al (2003) Neuropilin-1-mediated vascular permeability factor/vascular endothelial growth factor-dependent endothelial cell migration. J Biol Chem 278(49):48848–48860

    Article  PubMed  CAS  Google Scholar 

  50. Cai H, Reed RR (1999) Cloning and characterization of neuropilin-1-interacting protein: a PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of neuropilin-1. J Neurosci 19(15):6519–6527

    PubMed  CAS  Google Scholar 

  51. Chittenden TW et al (2006) Selective regulation of arterial branching morphogenesis by synectin. Dev Cell 10(6):783–795

    Article  PubMed  CAS  Google Scholar 

  52. Gao Y et al (2000) Synectin, syndecan-4 cytoplasmic domain binding PDZ protein, inhibits cell migration. J Cell Physiol 184(3):373–379

    Article  PubMed  CAS  Google Scholar 

  53. Wang L, Mukhopadhyay D, Xu X (2006) C terminus of RGS-GAIP-interacting protein conveys neuropilin-1-mediated signaling during angiogenesis. Faseb J 20(9):1513–1515

    Article  PubMed  CAS  Google Scholar 

  54. Goishi K, Klagsbrun M (2004) Vascular endothelial growth factor and its receptors in embryonic zebrafish blood vessel development. Curr Top Dev Biol 62:127–152

    PubMed  CAS  Google Scholar 

  55. Lee P et al (2002) Neuropilin-1 is required for vascular development and is a mediator of VEGF-dependent angiogenesis in zebrafish. Proc Natl Acad Sci USA 99(16):10470–10475

    Article  PubMed  CAS  Google Scholar 

  56. Eichmann A et al (2005) Vascular development: from precursor cells to branched arterial and venous networks. Int J Dev Biol 49(2–3):259–267

    Article  PubMed  CAS  Google Scholar 

  57. Herzog Y et al (2001) Differential expression of neuropilin-1 and neuropilin-2 in arteries and veins. Mech Dev 109(1):115–119

    Article  PubMed  CAS  Google Scholar 

  58. Yaniv K et al (2006) Live imaging of lymphatic development in the zebrafish. Nat Med 12(6):711–716

    Article  PubMed  CAS  Google Scholar 

  59. Yuan L et al (2002) Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development 129(20):4797–4806

    PubMed  CAS  Google Scholar 

  60. Kitsukawa T et al (1995) Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs. Development 121(12):4309–4318

    PubMed  CAS  Google Scholar 

  61. Kawasaki T et al (1999) A requirement for neuropilin-1 in embryonic vessel formation. Development 126(21):4895–4902

    PubMed  CAS  Google Scholar 

  62. Takashima S et al (2002) Targeting of both mouse neuropilin-1 and neuropilin-2 genes severely impairs developmental yolk sac and embryonic angiogenesis. Proc Natl Acad Sci USA 99(6):3657–3662

    Article  PubMed  CAS  Google Scholar 

  63. Chan J et al (2002) Dissection of angiogenic signaling in zebrafish using a chemical genetic approach. Cancer Cell 1(3):257–267

    Article  PubMed  CAS  Google Scholar 

  64. Mukouyama YS et al (2005) Peripheral nerve-derived VEGF promotes arterial differentiation via neuropilin 1-mediated positive feedback. Development 132(5):941–952

    Article  PubMed  CAS  Google Scholar 

  65. Miao HQ et al (2000) Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression. Faseb J 14(15):2532–2539

    Article  PubMed  CAS  Google Scholar 

  66. Parikh AA et al (2004) Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis. Am J Pathol 164(6):2139–2151

    PubMed  CAS  Google Scholar 

  67. Wey JS et al (2005) Overexpression of neuropilin-1 promotes constitutive MAPK signalling and chemoresistance in pancreatic cancer cells. Br J Cancer 93(2):233–241

    Article  PubMed  CAS  Google Scholar 

  68. Hong TM et al (2007) Targeting neuropilin 1 as an antitumor strategy in lung cancer. Clin Cancer Res 13(16):4759–4768

    Article  PubMed  CAS  Google Scholar 

  69. Baba T et al (2007) Neuropilin-1 promotes unlimited growth of ovarian cancer by evading contact inhibition. Gynecol Oncol 105(3):703–711

    Article  PubMed  CAS  Google Scholar 

  70. Handa A et al (2000) Neuropilin-2 expression affects the increased vascularization and is a prognostic factor in osteosarcoma. Int J Oncol 17(2):291–295

    PubMed  CAS  Google Scholar 

  71. Hansel DE et al (2004) Expression of neuropilin-1 in high-grade dysplasia, invasive cancer, and metastases of the human gastrointestinal tract. Am J Surg Pathol 28(3):347–356

    Article  PubMed  Google Scholar 

  72. Kawakami T et al (2002) Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma. Cancer 95(10):2196–2201

    Article  PubMed  CAS  Google Scholar 

  73. Kreuter M et al (2006) Correlation of neuropilin-1 overexpression to survival in acute myeloid leukemia. Leukemia 20(11):1950–1954

    Article  PubMed  CAS  Google Scholar 

  74. Lantuejoul S et al (2003) Expression of VEGF, semaphorin SEMA3F, and their common receptors neuropilins NP1 and NP2 in preinvasive bronchial lesions, lung tumours, and cell lines. J Pathol 200(3):336–347

    Article  PubMed  CAS  Google Scholar 

  75. Latil A et al (2000) VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms. Int J Cancer 89(2):167–171

    Article  PubMed  CAS  Google Scholar 

  76. Osada H et al (2004) Overexpression of the neuropilin 1 (NRP1) gene correlated with poor prognosis in human glioma. Anticancer Res 24(2B):547–552

    PubMed  CAS  Google Scholar 

  77. Sanchez-Carbayo M et al (2003) Gene discovery in bladder cancer progression using cDNA microarrays. Am J Pathol 163(2):505–516

    PubMed  CAS  Google Scholar 

  78. Vanveldhuizen PJ et al (2003) Differential expression of neuropilin-1 in malignant and benign prostatic stromal tissue. Oncol Rep 10(5):1067–1071

    PubMed  CAS  Google Scholar 

  79. Broholm H, Laursen H (2004) Vascular endothelial growth factor (VEGF) receptor neuropilin-1’s distribution in astrocytic tumors. Apmis 112(4–5):257–263

    Article  PubMed  CAS  Google Scholar 

  80. Ochiumi T et al (2006) Neuropilin-1 is involved in regulation of apoptosis and migration of human colon cancer. Int J Oncol 29(1):105–116

    PubMed  CAS  Google Scholar 

  81. Osada R et al (2006) Expression of semaphorins, vascular endothelial growth factor, and their common receptor neuropilins and alleic loss of semaphorin locus in epithelial ovarian neoplasms: increased ratio of vascular endothelial growth factor to semaphorin is a poor prognostic factor in ovarian carcinomas. Hum Pathol 37(11):1414–1425

    Article  PubMed  CAS  Google Scholar 

  82. Klein R et al (2007) Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology 114(2):253–262

    Article  PubMed  Google Scholar 

  83. Wang JJ et al (2007) The LOC387715 Polymorphism, inflammatory markers, smoking, and age-related macular degeneration a population-based case-control study. Ophthalmology

  84. Fletcher EC, Chong NV (2008) Looking beyond Lucentis on the management of macular degeneration. Eye. doi:10.1038/sj.eye.6703008

  85. Lien S, Lowman HB (2008) Therapeutic anti-VEGF antibodies. Handb Exp Pharmacol 181:131–150

    Article  PubMed  CAS  Google Scholar 

  86. Ishida S et al (2000) Coexpression of VEGF receptors VEGF-R2 and neuropilin-1 in proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 41(7):1649–1656

    PubMed  CAS  Google Scholar 

  87. Sekido Y et al (1996) Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns. Proc Natl Acad Sci USA 93(9):4120–4125

    Article  PubMed  CAS  Google Scholar 

  88. Tse C et al (2002) Human Semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line. Cancer Res 62(2):542–546

    PubMed  CAS  Google Scholar 

  89. Castro-Rivera E et al (2004) Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect. Proc Natl Acad Sci USA 101(31):11432–11437

    Article  PubMed  CAS  Google Scholar 

  90. Kessler O et al (2004) Semaphorin-3F is an inhibitor of tumor angiogenesis. Cancer Res 64(3):1008–1015

    Article  PubMed  CAS  Google Scholar 

  91. Bielenberg DR et al (2004) Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype. J Clin Invest 114(9):1260–1271

    PubMed  CAS  Google Scholar 

  92. Futamura M et al (2007) Possible role of semaphorin 3F, a candidate tumor suppressor gene at 3p21.3, in p53-regulated tumor angiogenesis suppression. Cancer Res 67(4):1451–1460

    Article  PubMed  CAS  Google Scholar 

  93. Jia H et al (2006) Characterization of a bicyclic peptide neuropilin-1 (NP-1) antagonist (EG3287) reveals importance of vascular endothelial growth factor exon 8 for NP-1 binding and role of NP-1 in KDR signaling. J Biol Chem 281(19):13493–13502

    Article  PubMed  CAS  Google Scholar 

  94. Siemion IZ, Kluczyk A (1999) Tuftsin: on the 30-year anniversary of Victor Najjar’s discovery. Peptides 20(5):645–674

    Article  PubMed  CAS  Google Scholar 

  95. Starzec A et al (2006) Antiangiogenic and antitumor activities of peptide inhibiting the vascular endothelial growth factor binding to neuropilin-1. Life Sci 79(25):2370–2381

    Article  PubMed  CAS  Google Scholar 

  96. Starzec A et al (2007) Structure-function analysis of the antiangiogenic ATWLPPR peptide inhibiting VEGF(165) binding to neuropilin-1 and molecular dynamics simulations of the ATWLPPR/neuropilin-1 complex. Peptides 28(12):2397–2402

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Melissa Herman for proofreading the manuscript and Kristin Johnson for technical assistance in figure preparation. This work was supported by National Institute of Health NCI grants CA37392 and CA45548 (to M.K.).

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Authors and Affiliations

  1. Department of Surgery, Vascular Biology Program, Children’s Hospital and Harvard Medical School, Karp Building 12210, 300 Longwood Ave., Boston, MA, 02115, USA

    Elena Geretti, Akio Shimizu & Michael Klagsbrun

  2. Department of Pathology, Vascular Biology Program, Children’s Hospital and Harvard Medical School, Karp Building 12210, 300 Longwood Ave., Boston, MA, 02115, USA

    Michael Klagsbrun

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  1. Elena Geretti
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Correspondence to Michael Klagsbrun.

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We dedicate this article to the memory of Dr. Judah Folkman, the leading pioneer of angiogenesis research.

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Geretti, E., Shimizu, A. & Klagsbrun, M. Neuropilin structure governs VEGF and semaphorin binding and regulates angiogenesis. Angiogenesis 11, 31–39 (2008). https://doi.org/10.1007/s10456-008-9097-1

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