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Integrin-binding peptide in solution inhibits or enhances endothelial cell migration, predictably from cell adhesion

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Abstract

We have examined the effects of an integrin-binding competitor, echistatin, in solution on adhesion and migration of rat microvessel endothelial cells on fibronectinin vitro. A biphasic dependence of cell motility on fibronectin surface density was observed, with a peak random motility coefficient of about 8 × 10−9 cm2/sec occurring below 0.3 μg/cm2 fibronectin. In the presence of echistatin at 0.5 μM, the peak random motility coefficient was similar but occurred at the significantly greater fibronectin surface density of 1.2 μg/cm2. Hence, the same concentration of this soluble integrin-binding competitor inhibited migration on low fibronectin densities but enhanced migration on high fibronectin densities. At the same time, echistatin decreased adhesiveness on all fibronectin surface densities. When motility was correlated explicitly with adhesiveness, a single biphasic relationship was obtained for both absence and presence of echistatin with peak motility occuring in both cases at identical adhesiveness. Both the inhibiting and enhancing effects of the soluble integrin-binding competitor on motility are predictable from its effect on adhesion, consistent with the theoretical models of Lauffenburger (15) and DiMillaet al. (3).

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References

  1. Boucaut, J.C.; Darribere, T.; Poole, T.J.; Aoyama, H.; Yamada, K.M.; Thiery, J.P. Biologically active synthetic peptides as probes of embryonic development: A competitive peptide inhibitor of fibronectin function inhibits gastrulation in amphibian embryos and neural crest cell migration. J. Cell Biol. 99:1822–1830; 1984.

    Article  CAS  PubMed  Google Scholar 

  2. Chu, L.; Tempelman, L.A.; Miller, C.; Hammer, D.A. Centrifugation assay for receptor-mediated cell adhesion of IgE-sensitized rat basophilic leukemia cells to antigencoated polyacrylamide gels. AIChE J. (accepted for publication).

  3. DiMilla, P.A.; Barbee, K.; Lauffenburger, D.A. Mathematical model for the effects of adhesion and mechanics on cell migration speed. Biophys. J. 60:15–37; 1991.

    CAS  PubMed  Google Scholar 

  4. DiMilla, P.A.; Albelda, S.M.; Quinn, J.A. Adsorption and elution of extracellular matrix proteins on non-tissue culture polystyrene petri dishes. J. Coll. Int. Sci. 153:212–225; 1992.

    Article  CAS  Google Scholar 

  5. DiMilla, P.A.; Stone, J.A.; Quinn, J.A.; Albelda, S.M.; Lauffenburger, D.A. An optimal adhesiveness exists for human smooth muscle cell migration on type IV collagen and fibronectin. J. Cell Biol. 122:729–737; 1993.

    Article  CAS  PubMed  Google Scholar 

  6. D'Souza, S.E.; Ginsberg, M.H.; Plow, E.F. Arginylglycyl-aspartic acid (RGD): a cell adhesion motif. Trends Biochem. Sci. 16:246–250; 1991.

    Article  PubMed  Google Scholar 

  7. Edelman, G.M.; Crossin, K.L. Cell adhesion molecules: Implications for a molecular histology. Annu. Rev. Biochem. 60:155–190; 1991.

    Article  CAS  PubMed  Google Scholar 

  8. Farrell, B.E.; Daniele, R.P.; Lauffenburger, D.A. Quantitative relationships between single-cell and cell-population model parameters for chemosensory migration responses of alveolar macrophages to C5a. Cell Motility Cytoskel. 16: 279–293; 1990.

    CAS  PubMed  Google Scholar 

  9. Gamble, J.R.; Matthias, L.J.; Meyer, G.; Kaur, P.; Russ, G.; Faull, R.; Berndt, M.C.; Vadas, M.A. Regulation ofin vitro capillary tube formation by anti-integrin antibodies. J. Cell Biol. 121:931–943; 1993.

    Article  CAS  PubMed  Google Scholar 

  10. Goodman, S.L.; Risse, G.; von der Mark, K. The E8 subfragment of laminin promotes locomotion of myoblasts over extracellular matrix. J. Cell Biol. 109:799–809; 1989.

    Article  CAS  PubMed  Google Scholar 

  11. Gould, R.J.; Polokoff, M.A.; Friedman, P.A.; Huang, T.-F.; Holt, J.C.; Cook, J.J.; Niewiarowski, S. Disintegrin. A family of integrin inhibitory proteins from viper venoms. Proc. Soc. Exp. Biol. Med. 195:168–171; 1990.

    CAS  PubMed  Google Scholar 

  12. Humphries, M.J.; Olden, K.; Yamada, K.M. A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science 233:457–470; 1986.

    Google Scholar 

  13. Ingber, D.E.; Folkman, J. How does extracellular matrix control capillary morphogenesis? Cell 59:803–805; 1989.

    Google Scholar 

  14. Larson, H.J. Introduction to Probability Theory and Statistical Inference, 3rd edition, New York: John Wiley & Sons, 1982, 637 pp.

    Google Scholar 

  15. Lauffenburger, D.A. A simple model for effects of receptormediated cell-substratum adhesion on cell migration. Chem. Eng. Sci. 44:1903–1914; 1989.

    CAS  Google Scholar 

  16. Lauffenburger, D.A.; Linderman, J.J. Receptors: Models for Binding, Trafficking, and Signaling. Oxford University Press, 1993, 365 pp.

  17. McClay, D.R.; Wessel, G.M.; Marchase, R.B. Intercellular recognition: Quantitation of initial binding events. Proc. Natl. Acad. Sci. 78:4975–4979; 1981.

    CAS  PubMed  Google Scholar 

  18. Nicosia, R.F.; Bonanno, E. Inhibition of angiogenesisin vitro by arg-gly-asp-containing synthetic peptide. Am. J. Pathol. 138:829–833; 1991.

    CAS  PubMed  Google Scholar 

  19. Nicosia, R.F.; Bonanno, E.; Smith, M. Fibronectin promotes the elongation of microvessels during angiogenesisin vitro. J. Cell. Physiol. 154:654–661; 1993.

    Article  CAS  PubMed  Google Scholar 

  20. Ruoslahti, E. Integrins. J. Clin. Invest. 87:1–5; 1991.

    CAS  PubMed  Google Scholar 

  21. Ruoslahti, E.; Giancotti, F.G. Integrins and tumor cell dissemination. Canc. Cells 1:119–126; 1989.

    CAS  Google Scholar 

  22. Ruoslahti, E.; Piersbacher, M.D. New perspectives in cell adhesion: RGD and integrins. Science 238:491–497; 1987.

    CAS  PubMed  Google Scholar 

  23. Rupnick, M.A.; Stokes, C.L.; Williams, S.K.; Lauffenburger, D.A. Quantitative analysis of random motility of human microvessel endothelial cells using a linear underagarose assay. Lab. Invest. 59:363–372; 1988.

    CAS  PubMed  Google Scholar 

  24. Savage, B.; Marzee, U.M.; Chao, B.H.; Harker, L.A.; Maraganore, J.M.; Ruggeri, Z.M. Binding of the snake venomderived proteins applaggin and echistatin to the arginineglycine-aspartic acid recognition site(s) on platelet glycoprotein IIb. IIIa complex inhibits receptor function. J. Biol. Chem. 265:11766–11772; 1990.

    CAS  PubMed  Google Scholar 

  25. Stokes, C.L.; Williams, S.K.; Lauffenburger, D.A. Migration of individual microvessel endothelial cells: Stochastic model and parameter measurement. J. Cell Sci. 99:419–430; 1991.

    PubMed  Google Scholar 

  26. Wagner, R.; Mathews, M. The isolation and culture of capillary endothelium from epididymal fat. Microvasc. Res. 10:286–297; 1975.

    Article  CAS  PubMed  Google Scholar 

  27. Williams, S.K. Isolation and culture of microvessel endothelial cells: their use in transplant and clinical studies. In: Microvascular Perfusion and Transplant in Health and Disease, edited by P. McDonagh. Basel, Switzerland: Karger, 1987, pp. 204–224.

    Google Scholar 

  28. Williams, S.K.; Jarrell, B.E.; Rose, D.G. Isolation of human fat-derived microvessel endothelial cells for use in vascular graft endothelialization. In: Endothelialization of Vascular Grafts, edited by P. Zilla, Basel, Switzerland: Karger, 1987, pp. 211–217.

    Google Scholar 

  29. Zigmond, S.H.; Lauffenburger, D.A. Assays for leukocyte chemotaxis. Annu. Rev. Med. 37:149–155; 1986.

    Article  CAS  PubMed  Google Scholar 

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Wu, P., Hoying, J.B., Williams, S.K. et al. Integrin-binding peptide in solution inhibits or enhances endothelial cell migration, predictably from cell adhesion. Ann Biomed Eng 22, 144–152 (1994). https://doi.org/10.1007/BF02390372

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  • DOI: https://doi.org/10.1007/BF02390372

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