VEGF and its receptors - formation, structure, and role in the organism
DOI:
https://doi.org/10.12775/JEHS.2023.21.01.019Keywords
VEGF, recepotrs, structure, functionAbstract
Creating vessels is essential for the development of every organism and the course of repair processes. Under physiological conditions, angiogenesis is a transient and tightly regulated process. Angiogenesis plays a significant role in the development of cancer and the progression of neoplastic diseases. The most well-known pro-angiogenic factors include the VEGF family, mainly VEGF-A. Of great interest in the angiogenesis process are the receptors for VEGF, both soluble and surface-bound.
The aim of this work is to elucidate the structure and mechanism of action of VEGF and its receptors.
References
Apte RS, Chen DS, Ferrara N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 2019 Mar 7;176(6):1248-1264. doi: 10.1016/j.cell.2019.01.021. PMID: 30849371; PMCID: PMC6410740.
Flournoy J, Ashkanani S, Chen Y. Mechanical regulation of signal transduction in angiogenesis. Front Cell Dev Biol. 2022 Aug 19;10:933474. doi: 10.3389/fcell.2022.933474. PMID: 36081909; PMCID: PMC9447863.
Siveen KS, Prabhu K, Krishnankutty R, Kuttikrishnan S, Tsakou M, Alali FQ, Dermime S, Mohammad RM, Uddin S. Vascular Endothelial Growth Factor (VEGF) Signaling in Tumour Vascularization: Potential and Challenges. Curr Vasc Pharmacol. 2017;15(4):339-351. doi: 10.2174/1570161115666170105124038. PMID: 28056756.
Shah AA, Kamal MA, Akhtar S. Tumor Angiogenesis and VEGFR-2: Mechanism, Pathways and Current Biological Therapeutic Interventions. Curr Drug Metab. 2021;22(1):50-59. doi: 10.2174/1389200221666201019143252. PMID: 33076807.
Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008 May 8;358(19):2039-49. doi: 10.1056/NEJMra0706596. PMID: 18463380; PMCID: PMC4542009.
Imhof BA, Aurrand-Lions M. Angiogenesis and inflammation face off. Nat Med. 2006 Feb;12(2):171-2. doi: 10.1038/nm0206-171. PMID: 16462798.
Mezu-Ndubuisi OJ, Maheshwari A. The role of integrins in inflammation and angiogenesis. Pediatr Res. 2021 May;89(7):1619-1626. doi: 10.1038/s41390-020-01177-9. Epub 2020 Oct 7. PMID: 33027803; PMCID: PMC8249239.
Bianconi D, Unseld M, Prager GW. Integrins in the Spotlight of Cancer. Int J Mol Sci. 2016 Dec 6;17(12):2037. doi: 10.3390/ijms17122037. PMID: 27929432; PMCID: PMC5187837
Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983 Feb 25;219(4587):983-5. doi: 10.1126/science.6823562. PMID: 6823562.
Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989 Jun 15;161(2):851-8. doi: 10.1016/0006-291x(89)92678-8. PMID: 2735925.
Plouët J, Schilling J, Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J. 1989 Dec 1;8(12):3801-6. doi: 10.1002/j.1460-2075.1989.tb08557.x. PMID: 2684646; PMCID: PMC402066.
Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003 Jun;9(6):669-76. doi: 10.1038/nm0603-669. PMID: 12778165.
Melincovici CS, Boşca AB, Şuşman S, Mărginean M, Mihu C, Istrate M, Moldovan IM, Roman AL, Mihu CM. Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis. Rom J Morphol Embryol. 2018;59(2):455-467. PMID: 30173249.
Markovic-Mueller S, Stuttfeld E, Asthana M, Weinert T, Bliven S, Goldie KN, Kisko K, Capitani G, Ballmer-Hofer K. Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A. Structure. 2017 Feb 7;25(2):341-352. doi: 10.1016/j.str.2016.12.012. Epub 2017 Jan 19. PMID: 28111021
Karaman S, Leppänen VM, Alitalo K. Vascular endothelial growth factor signaling in development and disease. Development. 2018 Jul 20;145(14):dev151019. doi: 10.1242/dev.151019. PMID: 30030240.
Albadari N, Deng S, Li W. The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy. Expert Opin Drug Discov. 2019 Jul;14(7):667-682. doi: 10.1080/17460441.2019.1613370. Epub 2019 May 9. PMID: 31070059; PMCID: PMC6559821.
Wiszniak S, Schwarz Q. Exploring the Intracrine Functions of VEGF-A. Biomolecules. 2021 Jan 19;11(1):128. doi: 10.3390/biom11010128. PMID: 33478167; PMCID: PMC7835749.
Davydova N, Harris NC, Roufail S, Paquet-Fifield S, Ishaq M, Streltsov VA, Williams SP, Karnezis T, Stacker SA, Achen MG. Differential Receptor Binding and Regulatory Mechanisms for the Lymphangiogenic Growth Factors Vascular Endothelial Growth Factor (VEGF)-C and -D. J Biol Chem. 2016 Dec 30;291(53):27265-27278. doi: 10.1074/jbc.M116.736801. Epub 2016 Nov 16. PMID: 27852824; PMCID: PMC5207153.
Mesquita J, Castro-de-Sousa JP, Vaz-Pereira S, Neves A, Passarinha LA, Tomaz CT. Vascular endothelial growth factors and placenta growth factor in retinal vasculopathies: Current research and future perspectives. Cytokine Growth Factor Rev. 2018 Feb;39:102-115. doi: 10.1016/j.cytogfr.2017.11.005. Epub 2017 Dec 7. PMID: 29248329.
Sammarco G, Varricchi G, Ferraro V, Ammendola M, De Fazio M, Altomare DF, Luposella M, Maltese L, Currò G, Marone G, Ranieri G, Memeo R. Mast Cells, Angiogenesis and Lymphangiogenesis in Human Gastric Cancer. Int J Mol Sci. 2019 Apr 29;20(9):2106. doi: 10.3390/ijms20092106. PMID: 31035644; PMCID: PMC6540185.
Goulart A, Ferreira C, Rodrigues A, Coimbra B, Sousa N, Leão P. The correlation between serum vascular endothelial growth factor (VEGF) and tumor VEGF receptor 3 in colorectal cancer. Ann Surg Treat Res. 2019 Jul;97(1):15-20. doi: 10.4174/astr.2019.97.1.15. Epub 2019 Jun 26. PMID: 31297348; PMCID: PMC6609416
Naderi S, Roshan R, Ghaderi H, Behdani M, Mahmoudi S, Habibi-Anbouhi M, Shokrgozar MA, Kazemi-Lomedasht F. Selection and characterization of specific nanobody against neuropilin-1 for inhibition of angiogenesis. Mol Immunol. 2020 Dec;128:56-63. doi: 10.1016/j.molimm.2020.10.004. Epub 2020 Oct 15. PMID: 33070092.
Shaik F, Cuthbert GA, Homer-Vanniasinkam S, Muench SP, Ponnambalam S, Harrison MA. Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy. Biomolecules. 2020 Dec 15;10(12):1673. doi: 10.3390/biom10121673. PMID: 33333800; PMCID: PMC7765180.
Heinolainen K, Karaman S, D'Amico G, Tammela T, Sormunen R, Eklund L, Alitalo K, Zarkada G. VEGFR3 Modulates Vascular Permeability by Controlling VEGF/VEGFR2 Signaling. Circ Res. 2017 Apr 28;120(9):1414-1425. doi: 10.1161/CIRCRESAHA.116.310477. Epub 2017 Mar 15. PMID: 28298294; PMCID: PMC6959003.
Tyrsina EG, Nikulitskiy SI, Inshakov AN, Ryabaya OO. VEGF-R1 as a Potential Molecular Target for Anticancer Therapy. Dokl Biochem Biophys. 2018 Jan;478(1):18-20. doi: 10.1134/S1607672918010052. Epub 2018 Mar 14. PMID: 29536302.
Kim KJ, Cho CS, Kim WU. Role of placenta growth factor in cancer and inflammation. Exp Mol Med. 2012 Jan 31;44(1):10-9. doi: 10.3858/emm.2012.44.1.023. PMID: 22217448; PMCID: PMC3277893.
Mamer SB, Wittenkeller A, Imoukhuede PI. VEGF-A splice variants bind VEGFRs with differential affinities. Sci Rep. 2020 Sep 2;10(1):14413. doi: 10.1038/s41598-020-71484-y. PMID: 32879419; PMCID: PMC7468149.
Shah AA, Kamal MA, Akhtar S. Tumor Angiogenesis and VEGFR-2: Mechanism, Pathways and Current Biological Therapeutic Interventions. Curr Drug Metab. 2021;22(1):50-59. doi: 10.2174/1389200221666201019143252. PMID: 33076807.
Grant DS, Kleinman HK. Regulation of capillary formation by laminin and other components of the extracellular matrix. EXS. 1997;79:317-33. doi: 10.1007/978-3-0348-9006-9_13. PMID: 9002225.
Ahmad A, Nawaz MI. Molecular mechanism of VEGF and its role in pathological angiogenesis. J Cell Biochem. 2022 Dec;123(12):1938-1965. doi: 10.1002/jcb.30344. Epub 2022 Oct 26. PMID: 36288574.
Cai J, Jiang WG, Grant MB, Boulton M. Pigment epithelium-derived factor inhibits angiogenesis via regulated intracellular proteolysis of vascular endothelial growth factor receptor 1. J Biol Chem. 2006 Feb 10;281(6):3604-13. doi: 10.1074/jbc.M507401200. Epub 2005 Dec 8. PMID: 16339148.
Failla CM, Carbo M, Morea V. Positive and Negative Regulation of Angiogenesis by Soluble Vascular Endothelial Growth Factor Receptor-1. Int J Mol Sci. 2018 Apr 27;19(5):1306. doi: 10.3390/ijms19051306. PMID: 29702562; PMCID: PMC5983705.
Karumanchi SA, Bdolah Y. Hypoxia and sFlt-1 in preeclampsia: the "chicken-and-egg" question. Endocrinology. 2004 Nov;145(11):4835-7. doi: 10.1210/en.2004-1028. PMID: 15489315.
Ambati BK, Patterson E, Jani P, Jenkins C, Higgins E, Singh N, Suthar T, Vira N, Smith K, Caldwell R. Soluble vascular endothelial growth factor receptor-1 contributes to the corneal antiangiogenic barrier. Br J Ophthalmol. 2007 Apr;91(4):505-8. doi: 10.1136/bjo.2006.107417. Epub 2006 Dec 6. Erratum in: Br J Ophthalmol. 2008 Mar;92(3):441-2. PMID: 17151056; PMCID: PMC1994740.
Kim NH, Oh JH, Seo JA, Lee KW, Kim SG, Choi KM, Baik SH, Choi DS, Kang YS, Han SY, Han KH, Ji YH, Cha DR. Vascular endothelial growth factor (VEGF) and soluble VEGF receptor FLT-1 in diabetic nephropathy. Kidney Int. 2005 Jan;67(1):167-77. doi: 10.1111/j.1523-1755.2005.00067.x. PMID: 15610240.
Jia H, Bagherzadeh A, Bicknell R, Duchen MR, Liu D, Zachary I. Vascular endothelial growth factor (VEGF)-D and VEGF-A differentially regulate KDR-mediated signaling and biological function in vascular endothelial cells. J Biol Chem. 2004 Aug 20;279(34):36148-57. doi: 10.1074/jbc.M401538200. Epub 2004 Jun 23. Erratum in: J Biol Chem. 2006 Feb 24;281(8):5328. PMID: 15215251.
Hoeres T, Wilhelm M, Smetak M, Holzmann E, Schulze-Tanzil G, Birkmann J. Immune cells regulate VEGF signalling via release of VEGF and antagonistic soluble VEGF receptor-1. Clin Exp Immunol. 2018 Apr;192(1):54-67. doi: 10.1111/cei.13090. Epub 2018 Jan 4. PMID: 29235095; PMCID: PMC5842402.
FT, Stefanini MO, Mac Gabhann F, Kontos CD, Annex BH, Popel AS. Computational kinetic model of VEGF trapping by soluble VEGF receptor-1: effects of transendothelial and lymphatic macromolecular transport. Physiol Genomics. 2009 Jun 10;38(1):29-41. doi: 10.1152/physiolgenomics.00031.2009. Epub 2009 Apr 7. PMID: 19351908; PMCID: PMC2696151.
Pavlakovic H, Becker J, Albuquerque R, Wilting J, Ambati J. Soluble VEGFR-2: an antilymphangiogenic variant of VEGF receptors. Ann N Y Acad Sci. 2010 Oct;1207 Suppl 1(Suppl 1):E7-15. doi: 10.1111/j.1749-6632.2010.05714.x. PMID: 20961309; PMCID: PMC3062194.
Stevens M, Oltean S. Modulation of Receptor Tyrosine Kinase Activity through Alternative Splicing of Ligands and Receptors in the VEGF-A/VEGFR Axis. Cells. 2019 Mar 28;8(4):288. doi: 10.3390/cells8040288. PMID: 30925751; PMCID: PMC6523102.
Wu FT, Stefanini MO, Mac Gabhann F, Kontos CD, Annex BH, Popel AS. A systems biology perspective on sVEGFR1: its biological function, pathogenic role and therapeutic use. J Cell Mol Med. 2010 Mar;14(3):528-52. doi: 10.1111/j.1582-4934.2009.00941.x. Epub 2009 Oct 16. PMID: 19840194; PMCID: PMC3039304.
Lorquet S, Berndt S, Blacher S, Gengoux E, Peulen O, Maquoi E, Noël A, Foidart JM, Munaut C, Péqueux C. Soluble forms of VEGF receptor-1 and -2 promote vascular maturation via mural cell recruitment. FASEB J. 2010 Oct;24(10):3782-95. doi: 10.1096/fj.09-149070. Epub 2010 May 19. PMID: 20484670.
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