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Gene Review

Vtn  -  vitronectin

Mus musculus

Synonyms: AI256434, S-protein, Serum-spreading factor, VN, Vitronectin, ...
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Disease relevance of Vtn

  • Intact vitronectin induces matrix metalloproteinase-2 and tissue inhibitor of metalloproteinases-2 expression and enhanced cellular invasion by melanoma cells [1].
  • Murine T lymphoma L5178Y-ML25 cells, which are known to metastasize to liver and spleen, preferentially adhered to vitronectin (VN) and migrated toward VN concentration gradients [2].
  • Plasminogen activator inhibitor 1 and vitronectin protect against stenosis in a murine carotid artery ligation model [3].
  • However, the role of VN in the earliest response to vascular injury, thrombosis, is not well characterized [4].
  • Three WT mice developed occlusive venous thrombosis an average of 39.7 +/- 1 minutes following the onset of injury, whereas the jugular veins of 4 mice deficient in PAI-1 and 4 deficient in VN occluded 56.7 +/- 5 and 58.7 +/- 2 minutes, respectively, following injury (P <.04 and P <.01 compared to WT mice) [5].
  • These findings provide a novel vitronectin-dependent mechanism contributing to the development of acute lung injury [6].

High impact information on Vtn


Chemical compound and disease context of Vtn


Biological context of Vtn

  • A detailed analysis of the molecular mechanisms involved in N1 and N7 cell adhesion to ECM substrata was performed by using antibodies raised against the FN receptor and synthetic peptides variously competing with the FN or VN binding to integrin receptor (GRGDSP and GRGESP) [16].
  • These observations suggest that OPN overproduction is advantageous to the metastatic phenotype, possibly by altering adhesion via, or signal transduction from, vitronectin receptors [17].
  • Furthermore, we have found that cell motility is enhanced by the availability of Vn in the matrix and that the AEC-Vn interaction is mediated, in part, by the alpha(v)beta(1) integrin [18].
  • Preincubation of beta-glucan with VN or FN enhanced macrophage activation in response to this cell wall component [19].
  • Activation of paxillin via Fn or Vn alone, or in combination, resulted in significantly lower phosphorylation signals compared to whole serum (41 +/- 6.9%, P < 0.05, 45 +/- 5.9%, P < 0.05, and 76 +/- 9.8%, P < 0.075, respectively) [20].

Anatomical context of Vtn

  • We anticipated that PAI-1 facilitated endothelial cell migration via its known interaction with vitronectin (VN) and integrins [21].
  • However, these anti-adhesive treatments, while ineffective on Vrest of N7 cells, abolished in N1 cells the FN- or VN-induced hyperpolarization and neurite outgrowth, that appeared therefore strictly associated and integrin-mediated phenomena [16].
  • Cellular invasiveness was also enhanced by vitronectin, as shown by the increased ability of vitronectin-treated cells to invade a synthetic basement membrane (Matrigel) [1].
  • Lymph node adhesion is mediated by an interaction between the tumor cell integrin alphavbeta3 and lymph node vitronectin [1].
  • In contrast, inhibition of ERK activation by PD98059 had no effect on the platelet-derived growth factor-regulated Rab4-dependent flux of alpha(v)beta(3) integrin from early endosomes to the plasma membrane, an event that is also necessary for cells to spread efficiently on vitronectin [22].

Associations of Vtn with chemical compounds

  • Antibodies, as well as GRGDSP, abolished adhesion of N1 and N7 clones to FN and VN, revealing a similar implication of integrins in the adhesion of these clones to the ECM proteins [16].
  • Both the vitronectin-induced MMP-2 production and vitronectin-enhanced invasion were blocked by the peptide ligand Arg-Gly-Asp-Ser (RGDS) [1].
  • The Arg-Gly-Asp (RGD)-containing peptide, a major adhesive ligand of ECM, is present in various plasma and matrix glycoproteins, such as FN and VN [11].
  • These studies indicate that VN and FN bind to beta-glucan components of P. carinii and augment macrophage inflammatory responses [19].
  • Vitronectin and fibronectin function as glucan binding proteins augmenting macrophage responses to Pneumocystis carinii [19].

Physical interactions of Vtn


Regulatory relationships of Vtn

  • Insulin-induced HUVEC migration and angiotube formation was also enhanced in the presence of VN and this enhancement is inhibited by PAI-1 [26].
  • The levels of phosphorylated cofilin were 10-fold higher in cells expressing alphavbeta3 than in alphavbeta3-negative cells when plated on vitronectin for 30 min [27].
  • Expression of alpha v beta 5 in tumor cells promoted their adhesion to vitronectin in vitro [28].
  • Addition of fibroblast growth factor markedly enhanced the survival of cells on the dishes coated with vitronectin or with fibronectin, but not on the dishes coated with heat-denatured bovine serum albumin [29].
  • These observations suggest that the S protein of MHV-JHM influences neurovirulence through the induction of MIP-1alpha- and MIP-1beta-driven macrophage immunopathology [30].

Other interactions of Vtn

  • However, using adenoviral gene transfer of PAI-1 mutants, we observed that PAI-1 promoted tumor angiogenesis, not by interacting with VN, but rather by inhibiting proteolytic activity, suggesting that excessive plasmin proteolysis prevents assembly of tumor vessels [21].
  • In this study, we explored the relationship between adhesion and proteolysis by examining the direct effect of vitronectin receptor ligation on matrix metalloproteinase-2 (MMP-2) production by B16F1 and B16F10 melanoma cells [1].
  • ERK1 associates with alpha(v)beta 3 integrin and regulates cell spreading on vitronectin [22].
  • We report a dose-dependent increase in secretion of both MMP-2 and tissue inhibitor of metalloproteinases-2 (TIMP-2) in response to vitronectin [1].
  • Plasminogen activator inhibitor type-1 inhibits insulin signaling by competing with alphavbeta3 integrin for vitronectin binding [26].

Analytical, diagnostic and therapeutic context of Vtn

  • In co-cultures on vitronectin of FN-null cells and beta(1)-null cells expressing a chimera with the extracellular domain of beta(1) and the cytoplasmic domain of beta(3), preferential assembly was by the chimera-expressing cells [31].
  • The cellular localization of liver Vn mRNA was studied by in situ hybridization [32].
  • Mouse vitronectin (Vn) was isolated from serum by heparin affinity chromatography [32].
  • Northern blot hybridization analysis of RNA from mouse tissues, using the mouse Vn cDNA as a hybridization probe, revealed the presence of a single transcript of 1.7 kilobases in mouse liver [32].
  • Southern blot analysis of DNA obtained from homozygous null mice demonstrates deletion of all VN coding sequences, and immunological analysis confirms the complete absence of VN protein expression in plasma [33].


  1. Intact vitronectin induces matrix metalloproteinase-2 and tissue inhibitor of metalloproteinases-2 expression and enhanced cellular invasion by melanoma cells. Bafetti, L.M., Young, T.N., Itoh, Y., Stack, M.S. J. Biol. Chem. (1998) [Pubmed]
  2. A new type of antimetastatic peptide derived from fibronectin. Kato, R., Ishikawa, T., Kamiya, S., Oguma, F., Ueki, M., Goto, S., Nakamura, H., Katayama, T., Fukai, F. Clin. Cancer Res. (2002) [Pubmed]
  3. Plasminogen activator inhibitor 1 and vitronectin protect against stenosis in a murine carotid artery ligation model. de Waard, V., Arkenbout, E.K., Carmeliet, P., Lindner, V., Pannekoek, H. Arterioscler. Thromb. Vasc. Biol. (2002) [Pubmed]
  4. Vitronectin inhibits the thrombotic response to arterial injury in mice. Fay, W.P., Parker, A.C., Ansari, M.N., Zheng, X., Ginsburg, D. Blood (1999) [Pubmed]
  5. Plasminogen activator inhibitor-1 and vitronectin promote vascular thrombosis in mice. Eitzman, D.T., Westrick, R.J., Nabel, E.G., Ginsburg, D. Blood (2000) [Pubmed]
  6. Involvement of vitronectin in lipopolysaccaride-induced acute lung injury. Tsuruta, Y., Park, Y.J., Siegal, G.P., Liu, G., Abraham, E. J. Immunol. (2007) [Pubmed]
  7. Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes. Chavakis, T., Hussain, M., Kanse, S.M., Peters, G., Bretzel, R.G., Flock, J.I., Herrmann, M., Preissner, K.T. Nat. Med. (2002) [Pubmed]
  8. Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages. Freire-de-Lima, C.G., Nascimento, D.O., Soares, M.B., Bozza, P.T., Castro-Faria-Neto, H.C., de Mello, F.G., DosReis, G.A., Lopes, M.F. Nature (2000) [Pubmed]
  9. Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization. Hammes, H.P., Brownlee, M., Jonczyk, A., Sutter, A., Preissner, K.T. Nat. Med. (1996) [Pubmed]
  10. Deletion of beta 1 integrins in mice results in inner cell mass failure and peri-implantation lethality. Stephens, L.E., Sutherland, A.E., Klimanskaya, I.V., Andrieux, A., Meneses, J., Pedersen, R.A., Damsky, C.H. Genes Dev. (1995) [Pubmed]
  11. Inhibition of metastatic cell colonization in murine lungs and tumor-induced morbidity by non-peptidic Arg-Gly-Asp mimetics. Hardan, I., Weiss, L., Hershkoviz, R., Greenspoon, N., Alon, R., Cahalon, L., Reich, S., Slavin, S., Lider, O. Int. J. Cancer (1993) [Pubmed]
  12. Promotion of malignant astrocytoma cell migration by osteopontin expressed in the normal brain: differences in integrin signaling during cell adhesion to osteopontin versus vitronectin. Ding, Q., Stewart, J., Prince, C.W., Chang, P.L., Trikha, M., Han, X., Grammer, J.R., Gladson, C.L. Cancer Res. (2002) [Pubmed]
  13. Effects of the novel alphav integrin antagonist SM256 and cis-platinum on growth of murine squamous cell carcinoma PAM LY8. Van Waes, C., Enamorado-Ayala, I., Hecht, D., Sulica, L., Chen, Z., Batt, D.G., Mousa, S. Int. J. Oncol. (2000) [Pubmed]
  14. Thrombotic phenotype of mice with a combined deficiency in plasminogen activator inhibitor 1 and vitronectin. Koschnick, S., Konstantinides, S., Schäfer, K., Crain, K., Loskutoff, D.J. J. Thromb. Haemost. (2005) [Pubmed]
  15. Isolation and characterization of murine clonogenic osteoclast progenitors by cell surface phenotype analysis. Muguruma, Y., Lee, M.Y. Blood (1998) [Pubmed]
  16. Integrin-mediated neurite outgrowth in neuroblastoma cells depends on the activation of potassium channels. Arcangeli, A., Becchetti, A., Mannini, A., Mugnai, G., De Filippi, P., Tarone, G., Del Bene, M.R., Barletta, E., Wanke, E., Olivotto, M. J. Cell Biol. (1993) [Pubmed]
  17. Specific reduction in osteopontin synthesis by antisense RNA inhibits the tumorigenicity of transformed Rat1 fibroblasts. Gardner, H.A., Berse, B., Senger, D.R. Oncogene (1994) [Pubmed]
  18. Plasminogen activator inhibitor-1 impairs alveolar epithelial repair by binding to vitronectin. Lazar, M.H., Christensen, P.J., Du, M., Yu, B., Subbotina, N.M., Hanson, K.E., Hansen, J.M., White, E.S., Simon, R.H., Sisson, T.H. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  19. Vitronectin and fibronectin function as glucan binding proteins augmenting macrophage responses to Pneumocystis carinii. Vassallo, R., Kottom, T.J., Standing, J.E., Limper, A.H. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  20. Differential phosphorylation of paxillin in response to surface-bound serum proteins during early osteoblast adhesion. Sommerfeldt, D.W., McLeod, K.J., Rubin, C.T., Hadjiargyrou, M. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  21. The plasminogen activator inhibitor PAI-1 controls in vivo tumor vascularization by interaction with proteases, not vitronectin. Implications for antiangiogenic strategies. Bajou, K., Masson, V., Gerard, R.D., Schmitt, P.M., Albert, V., Praus, M., Lund, L.R., Frandsen, T.L., Brunner, N., Dano, K., Fusenig, N.E., Weidle, U., Carmeliet, G., Loskutoff, D., Collen, D., Carmeliet, P., Foidart, J.M., Noël, A. J. Cell Biol. (2001) [Pubmed]
  22. ERK1 associates with alpha(v)beta 3 integrin and regulates cell spreading on vitronectin. Roberts, M.S., Woods, A.J., Shaw, P.E., Norman, J.C. J. Biol. Chem. (2003) [Pubmed]
  23. Cell cycle-mediated regulation of smooth muscle alpha-actin gene transcription in fibroblasts and vascular smooth muscle cells involves multiple adenovirus E1A-interacting cofactors. Wang, S.X., Elder, P.K., Zheng, Y., Strauch, A.R., Kelm, R.J. J. Biol. Chem. (2005) [Pubmed]
  24. Assay of oxysterol-binding protein in a mouse fibroblast, cell-free system. Dissociation constant and other properties of the system. Kandutsch, A.A., Shown, E.P. J. Biol. Chem. (1981) [Pubmed]
  25. Conformational lability of vitronectin: induction of an antigenic change by alpha-thrombin-serpin complexes and by proteolytically modified thrombin. Tomasini, B.R., Owen, M.C., Fenton, J.W., Mosher, D.F. Biochemistry (1989) [Pubmed]
  26. Plasminogen activator inhibitor type-1 inhibits insulin signaling by competing with alphavbeta3 integrin for vitronectin binding. López-Alemany, R., Redondo, J.M., Nagamine, Y., Muñoz-Cánoves, P. Eur. J. Biochem. (2003) [Pubmed]
  27. Alphavbeta3 integrin and cofilin modulate K1735 melanoma cell invasion. Dang, D., Bamburg, J.R., Ramos, D.M. Exp. Cell Res. (2006) [Pubmed]
  28. Insulin-like growth factor receptor cooperates with integrin alpha v beta 5 to promote tumor cell dissemination in vivo. Brooks, P.C., Klemke, R.L., Schon, S., Lewis, J.M., Schwartz, M.A., Cheresh, D.A. J. Clin. Invest. (1997) [Pubmed]
  29. Survival of 3T3-L1 cells induced by fibroblast growth factor depends on cell density and adhesion to the substratum. Shiba, Y., Yamada, S., Kanno, Y. Cell Struct. Funct. (1989) [Pubmed]
  30. Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology. Rempel, J.D., Murray, S.J., Meisner, J., Buchmeier, M.J. Virology (2004) [Pubmed]
  31. Assembly of exogenous fibronectin by fibronectin-null cells is dependent on the adhesive substrate. Bae, E., Sakai, T., Mosher, D.F. J. Biol. Chem. (2004) [Pubmed]
  32. Detection of vitronectin mRNA in tissues and cells of the mouse. Seiffert, D., Keeton, M., Eguchi, Y., Sawdey, M., Loskutoff, D.J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  33. Vitronectin is not essential for normal mammalian development and fertility. Zheng, X., Saunders, T.L., Camper, S.A., Samuelson, L.C., Ginsburg, D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
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