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Gene Review

VTN  -  vitronectin

Homo sapiens

Synonyms: S-protein, Serum-spreading factor, V75, VN, VNT, ...
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Disease relevance of VTN

  • On the other hand, uPA treatment strongly increases the adhesion of anaplastic carcinoma cells specifically to VTN [1].
  • The purified globulin inhibited spreading of osteosarcoma and melanoma cells on vitronectin, and of endothelial cells, platelets, and mononuclear blood cells on vitronectin or fibrinogen [2].
  • Staining of lung biopsy specimens from patients with acute lung injury indicated that fibrin and vitronectin colocalize at exudative sites in which macrophages bearing these receptors accumulate [3].
  • Although the role of VN as a permissive substrate for glioma migration has been well characterized, its role in conferring a survival advantage for tumor cells has not been addressed previously [4].
  • VN, an ECM protein preferentially expressed at the tumor-brain interface in vivo, may confer a survival advantage to glioma cells at the advancing tumor margin and may thus, in part, underlie the high level of tumor recurrence at this interface [4].

Psychiatry related information on VTN


High impact information on VTN

  • This receptor appears to mediate cell adhesion to vitronectin as well as fibronectin since an antibody directed to its alpha subunit blocked carcinoma cell adhesion to both of these matrix proteins [6].
  • The urokinase-type plasminogen activator receptor (uPAR) and integrins formed stable complexes that both inhibited native integrin adhesive function and promoted adhesion to vitronectin via a ligand binding site on uPAR [7].
  • These results indicate that a rise in [Ca2+]i reduces integrin-mediated adhesion to vitronectin by a mechanism that requires calcineurin activity [8].
  • Migration of human polymorphonuclear neutrophils on vitronectin is dependent on repeated transient increases in the concentration of intracellular free calcium ([Ca2+]i) [8].
  • A similar reduction in motility on vitronectin occurred when cells were treated with the immunosuppressant FK506, which also inhibits calcineurin when bound to its binding protein, FKBP [8].

Chemical compound and disease context of VTN

  • We have reported that metastatic human melanoma cells utilize the alpha (v)beta3 integrin to adhere to lymph node vitronectin (VN) [9].
  • Likewise, unlabeled human fibronectin and heparin inhibited the binding of labeled S protein to group G streptococci, S. aureus, and E. coli, but did not influence the binding to group A and C streptococci [10].
  • The binding to group G streptococci, S. aureus, and E. coli is mediated in part through a domain in the S protein containing the sequence Arg-Gly-Asp, whereas a different site is responsible for the binding to group A and C streptococci [10].
  • We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast [11].
  • We demonstrate here that endodermal sinus tumour cells, but not other cell types isolated from testicular teratomas, secrete the serum attachment protein, vitronectin (also known as serum-spreading factor, S-protein or epibolin), as well as fibronectin, laminin and type IV collagen, into serum-free medium [12].

Biological context of VTN

  • The prolongation of uPA treatment increases cell adhesion to VTN, and, less efficiently, to other ECM components [13].
  • The uPA-induced increase in MCF-7 cell migration was observed selectively on vitronectin-coated surfaces and was mediated by a beta1-integrin (probably alphaVbeta1) and alphaVbeta5 [14].
  • S 36578-2 is highly selective for alphavbeta3 and alphavbeta5 integrins and induces detachment, caspase-8 activation, and apoptosis in human umbilical endothelial cells (HUVECs) plated on vitronectin [15].
  • The identification of platelet VN and its binding to platelet PAI-1 raises the possibility that VN, in contrast to other adhesive proteins, may participate in localized regulatory functions of blood coagulation and fibrinolysis in platelet-matrix interactions and the protection of the matrix against proteolysis [16].
  • The augmentation of phagocytosis of EA induced by vitronectin could be inhibited by the F(ab')2 fragments of anti-vitronectin IgG but not by preimmune F(ab')2 [17].

Anatomical context of VTN

  • We have previously shown that uPA-R is involved in the adhesion of normal thyroid cells to VTN [13].
  • Fibronectin and vitronectin regulate the organization of their respective Arg-Gly-Asp adhesion receptors in cultured human endothelial cells [18].
  • Induction of Mac-1 and uPAR expression on monocytic cell lines by transforming growth factor- beta 1 and 1.25-(OH)2 vitamin D3 conferred urokinase and uPAR-dependent adhesion to vitronectin, which was further promoted by engagement of Mac-1 [3].
  • These studies demonstrate that vitronectin modulates interactions between monocytes and opsonized particles [17].
  • Here, we demonstrate that Zn2+ can induce the adhesion of myelomonocytic cells to the endothelium, as well as to the provisional matrix proteins vitronectin (VN) and fibrinogen (FBG), which are pivotal steps for the recruitment of leukocytes into inflamed/injured tissue [19].

Associations of VTN with chemical compounds

  • In keeping with the persistence of HCs in tissues during therapy, such killing was inhibited by integrin-mediated adhesion to vitronectin or fibronectin [20].
  • However, when ECs were treated with monensin only the vn receptor was organized in adhesion structures while the fn receptor was diffusely distributed [21].
  • Deposition was greater when platelets were adherent to FN than to VN and was elicited by platelet agonists with the following order of potency: thrombin > LPA = ADP (adenosine diphosphate) > S1P [22].
  • The adhesive glycoprotein vitronectin (VN) forms a function-stabilizing complex with plasminogen activator inhibitor-1 (PAI-1), the major fibrinolysis inhibitor in both plasma and vessel wall connective tissue [23].
  • These results suggest that the cell-binding and PAI-1 binding sequences of Vn occupy distinct regions in the NH2-terminal somatomedin B domain of the molecule [24].
  • Alphavbeta3 integrin was identified as the major cellular receptor for vitronectin-mediated adherence and uptake of pneumococci [25].

Physical interactions of VTN

  • Both receptors promote degradation of fibrin(ogen) and also confer adhesive properties on cells because Mac-1 and uPAR bind fibrin and vitronectin, respectively [3].
  • Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin) [26].
  • Here we report that the peptide GPIIb alpha 300-312 (G13) inhibits platelet aggregation and binds Fg and Vn [27].
  • Only bacterial strains with significant S protein binding but weak fibronectin binding were included in these studies [28].
  • These studies were conducted to determine if vitronectin bound IGFBP-5 with high affinity and if this altered the ability of either protein to modify cellular responsiveness to IGF-I [29].

Enzymatic interactions of VTN


Co-localisations of VTN

  • CK2 localization at the cell surface was highly dynamic; Vn induced formation of clusters where CK2 colocalized with uPAR and alpha(v)beta(3) integrins [30].
  • CLSM image analysis confirmed that the b-Vn was internalized and that it colocalized with PAI-1 in storage granules [34].
  • Clusterin protein colocalized with the membrane attack complex of complement and vitronectin in the center of the largest Hassal's bodies, but was not detectable by immunocytochemistry in or at the surface of epithelial cells [35].

Regulatory relationships of VTN


Other interactions of VTN

  • The shape of receptor clusters was slightly different and a colocalization of the two receptors was found when ECs were cultured on a mixed matrix of fn plus vn [18].
  • Together, these results suggest a VN-independent, uPA-uPAR-dependent mechanism by which PAI-1 induces cell detachment [41].
  • Through these interactions, HKa or its recombinant His-Gly-Lys-rich domain 5 completely inhibited the uPAR-dependent adhesion of myelomonocytic U937 cells and uPAR-transfected BAF-3 cells to VN and thereby promoted cell detachment [42].
  • Thus, VN-mediated uPA binding to cells was regulated by the ratio of soluble to surface-associated uPAR [43].
  • No evidence for adhesion to vitronectin through CD29 and beta 5 integrins was obtained [44].

Analytical, diagnostic and therapeutic context of VTN

  • A specific enzyme-linked immunosorbent assay (ELISA) for VN has been developed and was used to detect and to quantitate VN in detergent extracts of washed platelets with 8.1 +/- 4.6 micrograms/10(9) platelets (n = 10), representing about 0.8% of the plasma VN pool [16].
  • Platelet and plasma VN were similar by immunochemical criteria using Western-blot analysis, although platelet VN was mainly found as partially proteolyzed polypeptide [16].
  • By immunogold electron microscopy, both VN and HK/HKa were found to be colocalized in sections from human atherosclerotic coronary artery, indicating that the described interactions are likely to take place in vivo [42].
  • The gel filtration behavior, mobility on sodium dodecyl sulfate-gel electrophoresis, and concentration in plasma suggest that PAI-1-BP is a multimer (presumably a dimer) of S protein accounting for approximately 35% of the S protein in plasma [26].
  • Specific immunoprecipitation of newly synthesized urokinase indicated that cells adherent to fibronectin synthesized 2-3-fold more urokinase than cells adherent to vitronectin [45].


  1. Differential expression of a truncated form of the urokinase-type plasminogen-activator receptor in normal and tumor thyroid cells. Ragno, P., Montuori, N., Covelli, B., Hoyer-Hansen, G., Rossi, G. Cancer Res. (1998) [Pubmed]
  2. Inhibition of cell adhesion by high molecular weight kininogen. Asakura, S., Hurley, R.W., Skorstengaard, K., Ohkubo, I., Mosher, D.F. J. Cell Biol. (1992) [Pubmed]
  3. Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on monocytic cells. Simon, D.I., Rao, N.K., Xu, H., Wei, Y., Majdic, O., Ronne, E., Kobzik, L., Chapman, H.A. Blood (1996) [Pubmed]
  4. Vitronectin, a glioma-derived extracellular matrix protein, protects tumor cells from apoptotic death. Uhm, J.H., Dooley, N.P., Kyritsis, A.P., Rao, J.S., Gladson, C.L. Clin. Cancer Res. (1999) [Pubmed]
  5. Integrin alpha(v)beta(3) mediates rotavirus cell entry. Guerrero, C.A., Méndez, E., Zárate, S., Isa, P., López, S., Arias, C.F. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  6. A novel vitronectin receptor integrin (alpha v beta x) is responsible for distinct adhesive properties of carcinoma cells. Cheresh, D.A., Smith, J.W., Cooper, H.M., Quaranta, V. Cell (1989) [Pubmed]
  7. Regulation of integrin function by the urokinase receptor. Wei, Y., Lukashev, M., Simon, D.I., Bodary, S.C., Rosenberg, S., Doyle, M.V., Chapman, H.A. Science (1996) [Pubmed]
  8. Inhibition of neutrophil chemokinesis on vitronectin by inhibitors of calcineurin. Hendey, B., Klee, C.B., Maxfield, F.R. Science (1992) [Pubmed]
  9. Integrin alpha3beta1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma. Tawil, N.J., Gowri, V., Djoneidi, M., Nip, J., Carbonetto, S., Brodt, P. Int. J. Cancer (1996) [Pubmed]
  10. Specific binding of the human S protein (vitronectin) to streptococci, Staphylococcus aureus, and Escherichia coli. Chhatwal, G.S., Preissner, K.T., Müller-Berghaus, G., Blobel, H. Infect. Immun. (1987) [Pubmed]
  11. Vitronectin in human breast carcinomas. Aaboe, M., Offersen, B.V., Christensen, A., Andreasen, P.A. Biochim. Biophys. Acta (2003) [Pubmed]
  12. Vitronectin production by human yolk sac carcinoma cells resembling parietal endoderm. Cooper, S., Pera, M.F. Development (1988) [Pubmed]
  13. Urokinase-type plasminogen-activator and normal thyroid cell adhesion to the extracellular matrix. Ragno, P., Montuori, N., Salzano, S., Rossi, G. Biochimie (1999) [Pubmed]
  14. Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. Nguyen, D.H., Catling, A.D., Webb, D.J., Sankovic, M., Walker, L.A., Somlyo, A.V., Weber, M.J., Gonias, S.L. J. Cell Biol. (1999) [Pubmed]
  15. Blockade of {alpha}vbeta3 and {alpha}vbeta5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells. Maubant, S., Saint-Dizier, D., Boutillon, M., Perron-Sierra, F., Casara, P.J., Hickman, J.A., Tucker, G.C., Van Obberghen-Schilling, E. Blood (2006) [Pubmed]
  16. Identification of and partial characterization of platelet vitronectin: evidence for complex formation with platelet-derived plasminogen activator inhibitor-1. Preissner, K.T., Holzhüter, S., Justus, C., Müller-Berghaus, G. Blood (1989) [Pubmed]
  17. Vitronectin (S protein) augments the functional activity of monocyte receptors for IgG and complement C3b. Parker, C.J., Frame, R.N., Elstad, M.R. Blood (1988) [Pubmed]
  18. Fibronectin and vitronectin regulate the organization of their respective Arg-Gly-Asp adhesion receptors in cultured human endothelial cells. Dejana, E., Colella, S., Conforti, G., Abbadini, M., Gaboli, M., Marchisio, P.C. J. Cell Biol. (1988) [Pubmed]
  19. Molecular mechanisms of zinc-dependent leukocyte adhesion involving the urokinase receptor and beta2-integrins. Chavakis, T., May, A.E., Preissner, K.T., Kanse, S.M. Blood (1999) [Pubmed]
  20. Response of hairy cells to IFN-alpha involves induction of apoptosis through autocrine TNF-alpha and protection by adhesion. Baker, P.K., Pettitt, A.R., Slupsky, J.R., Chen, H.J., Glenn, M.A., Zuzel, M., Cawley, J.C. Blood (2002) [Pubmed]
  21. Fibrinogen induces endothelial cell adhesion and spreading via the release of endogenous matrix proteins and the recruitment of more than one integrin receptor. Dejana, E., Lampugnani, M.G., Giorgi, M., Gaboli, M., Marchisio, P.C. Blood (1990) [Pubmed]
  22. Assembly of a fibronectin matrix by adherent platelets stimulated by lysophosphatidic acid and other agonists. Olorundare, O.E., Peyruchaud, O., Albrecht, R.M., Mosher, D.F. Blood (2001) [Pubmed]
  23. A novel antithrombotic role for high molecular weight kininogen as inhibitor of plasminogen activator inhibitor-1 function. Chavakis, T., Pixley, R.A., Isordia-Salas, I., Colman, R.W., Preissner, K.T. J. Biol. Chem. (2002) [Pubmed]
  24. Evidence that type 1 plasminogen activator inhibitor binds to the somatomedin B domain of vitronectin. Seiffert, D., Loskutoff, D.J. J. Biol. Chem. (1991) [Pubmed]
  25. Integrin-linked kinase is required for vitronectin-mediated internalization of Streptococcus pneumoniae by host cells. Bergmann, S., Lang, A., Rohde, M., Agarwal, V., Rennemeier, C., Grashoff, C., Preissner, K.T., Hammerschmidt, S. J. Cell. Sci. (2009) [Pubmed]
  26. Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin). Declerck, P.J., De Mol, M., Alessi, M.C., Baudner, S., Pâques, E.P., Preissner, K.T., Müller-Berghaus, G., Collen, D. J. Biol. Chem. (1988) [Pubmed]
  27. A peptide corresponding to GPIIb alpha 300-312, a presumptive fibrinogen gamma-chain binding site on the platelet integrin GPIIb/IIIa, inhibits the adhesion of platelets to at least four adhesive ligands. Taylor, D.B., Gartner, T.K. J. Biol. Chem. (1992) [Pubmed]
  28. Mediation of adherence of streptococci to human endothelial cells by complement S protein (vitronectin). Valentin-Weigand, P., Grulich-Henn, J., Chhatwal, G.S., Müller-Berghaus, G., Blobel, H., Preissner, K.T. Infect. Immun. (1988) [Pubmed]
  29. Vitronectin binding to IGF binding protein-5 (IGFBP-5) alters IGFBP-5 modulation of IGF-I actions. Nam, T., Moralez, A., Clemmons, D. Endocrinology (2002) [Pubmed]
  30. Urokinase-dependent human vascular smooth muscle cell adhesion requires selective vitronectin phosphorylation by ectoprotein kinase CK2. Stepanova, V., Jerke, U., Sagach, V., Lindschau, C., Dietz, R., Haller, H., Dumler, I. J. Biol. Chem. (2002) [Pubmed]
  31. Modulation of heparin cofactor II function by S protein (vitronectin) and formation of a ternary S protein-thrombin-heparin cofactor II complex. Preissner, K.T., Sié, P. Thromb. Haemost. (1988) [Pubmed]
  32. Identification of a role of the vitronectin receptor and protein kinase C in the induction of endothelial cell vascular formation. Davis, C.M., Danehower, S.C., Laurenza, A., Molony, J.L. J. Cell. Biochem. (1993) [Pubmed]
  33. Integrin alpha v beta 5-dependent serine phosphorylation of paxillin in cultured human macrophages adherent to vitronectin. De Nichilo, M.O., Yamada, K.M. J. Biol. Chem. (1996) [Pubmed]
  34. Differential mechanisms targeting type 1 plasminogen activator inhibitor and vitronectin into the storage granules of a human megakaryocytic cell line. Hill, S.A., Shaughnessy, S.G., Joshua, P., Ribau, J., Austin, R.C., Podor, T.J. Blood (1996) [Pubmed]
  35. Distinct sites of production and deposition of the putative cell death marker clusterin in the human thymus. French, L.E., Sappino, A.P., Tschopp, J., Schifferli, J.A. J. Clin. Invest. (1992) [Pubmed]
  36. Successful silencing of plasminogen activator inhibitor-1 in human vascular endothelial cells using small interfering RNA. Hecke, A., Brooks, H., Meryet-Figuière, M., Minne, S., Konstantinides, S., Hasenfuss, G., Lebleu, B., Schäfer, K. Thromb. Haemost. (2006) [Pubmed]
  37. Vitronectin in human hepatic tumours contributes to the recruitment of lymphocytes in an alphavbeta3-independent manner. Edwards, S., Lalor, P.F., Tuncer, C., Adams, D.H. Br. J. Cancer (2006) [Pubmed]
  38. Plasminogen activator inhibitor type 1 promotes fibrosarcoma cell migration by modifying cellular attachment to vitronectin via alpha(v)beta(5) integrin. Takahashi, T., Suzuki, K., Ihara, H., Mogami, H., Kazui, T., Urano, T. Semin. Thromb. Hemost. (2005) [Pubmed]
  39. Matrix metalloproteinase-2 activation modulates glioma cell migration. Deryugina, E.I., Bourdon, M.A., Luo, G.X., Reisfeld, R.A., Strongin, A. J. Cell. Sci. (1997) [Pubmed]
  40. Alphavbeta integrins play an essential role in BMP-2 induction of osteoblast differentiation. Lai, C.F., Cheng, S.L. J. Bone Miner. Res. (2005) [Pubmed]
  41. Plasminogen activator inhibitor-1 detaches cells from extracellular matrices by inactivating integrins. Czekay, R.P., Aertgeerts, K., Curriden, S.A., Loskutoff, D.J. J. Cell Biol. (2003) [Pubmed]
  42. Different mechanisms define the antiadhesive function of high molecular weight kininogen in integrin- and urokinase receptor-dependent interactions. Chavakis, T., Kanse, S.M., Lupu, F., Hammes, H.P., Müller-Esterl, W., Pixley, R.A., Colman, R.W., Preissner, K.T. Blood (2000) [Pubmed]
  43. Vitronectin concentrates proteolytic activity on the cell surface and extracellular matrix by trapping soluble urokinase receptor-urokinase complexes. Chavakis, T., Kanse, S.M., Yutzy, B., Lijnen, H.R., Preissner, K.T. Blood (1998) [Pubmed]
  44. Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alpha v beta 3) integrin. Shimizu, Y., Irani, A.M., Brown, E.J., Ashman, L.K., Schwartz, L.B. Blood (1995) [Pubmed]
  45. Vitronectin regulates the synthesis and localization of urokinase-type plasminogen activator in HT-1080 cells. Ciambrone, G.J., McKeown-Longo, P.J. J. Biol. Chem. (1992) [Pubmed]
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