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Adhesion Molecules: Potential Therapeutic and Diagnostic Implications

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Anticoagulants, Antiplatelets, and Thrombolytics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 663))

Abstract

The role of cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins in various pathological processes, including angiogenesis, thrombosis, inflammation, apoptosis, cell migration, and proliferation is well documented. These processes can lead to both acute and chronic disease states such as ocular diseases, metastasis, unstable angina, myocardial infarction, stroke, osteoporosis, a wide range of inflammatory diseases, vascular remodeling, and neurodegenerative disorders. A key success in this field was identification of the role of platelet glycoprotein (GP)IIb/IIIa in the prevention and diagnosis of various thromboembolic disorders. The use of soluble adhesion molecules as potential diagnostic markers for acute and chronic leukocyte, platelet, and endothelial cell insult is becoming increasingly common. The development of various therapeutic and diagnostic candidates based on the key role of CAMs, with special emphasis on integrins in various diseases, as well as the structure–function aspects of cell adhesion and signaling of the different CAMs and ECM are highlighted.

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References

  1. Cox, D., Aoki, T., Seki, J., Motoyama, Y., and Yoshida, K. (1994) The pharmacology of the integrins Med Res Rev 14, 195–228.

    Article  PubMed  CAS  Google Scholar 

  2. Lal, H., Verma, S.K., Foster, D.M., Golden, H.B., Reneau, J.C., Watson, L.E., Singh, H., and Dostal, D.E. (2009) Integrins and proximal signaling mechanisms in cardiovascular disease Front Biosci 14, 2307–34.

    Article  PubMed  CAS  Google Scholar 

  3. Gold, H.K., Gimple, L.W., Yasuda, T., Leinbach, R.C., Werner, W., Holt, R., Jordan, R., Berger, H., Collen, D., and Coller, B.S. (1990) Pharmacodynamic study of F(ab’)2 fragments of murine monoclonal antibody 7E3 directed against human platelet glycoprotein IIb/IIIa in patients with unstable angina pectoris J Clin Invest 86, 651–9.

    Article  PubMed  CAS  Google Scholar 

  4. Mousa, S., and Topol, E. Novel antiplatelet therapies: recent advances in the development of platelet GPIIb/IIIa receptor antagonists. In: Serruys, P.W., and Holmes, D., eds. Current Review of Interventional Cardiology, 3rd edition. Philadelphia, PA: Current Medicine;1997:114–29.

    Google Scholar 

  5. Mousa, S.A., Bozarth, J.M., Forsythe, M.S., Jackson, S.M., Leamy, A., Diemer, M.M., Kapil, R.P., Knabb, R.M., Mayo, M.C., Pierce, S.K., et al. (1994) Antiplatelet and antithrombotic efficacy of DMP 728, a novel platelet GPIIb/IIIa receptor antagonist Circulation 89, 3–12.

    Article  PubMed  CAS  Google Scholar 

  6. Mousa, S.A., Bozarth, J.M., Forsythe, M.S., Lorelli, W., Thoolen, M.J., Ramachandran, N., Jackson, S., De Grado, W., and Reilly, T.M. (1993) Antiplatelet efficacy and specificity of DMP728, a novel platelet GPIIb/IIIa receptor antagonist Cardiology 83, 374–82.

    Article  PubMed  CAS  Google Scholar 

  7. van’t Hof, A.W., and Valgimigli, M. (2009) Defining the role of platelet glycoprotein receptor inhibitors in STEMI: focus on tirofiban Drugs 69, 85–100.

    Article  PubMed  Google Scholar 

  8. Brooks, P.C., Clark, R.A., and Cheresh, D.A. (1994) Requirement of vascular integrin alpha v beta 3 for angiogenesis Science 264, 569–71.

    Article  PubMed  CAS  Google Scholar 

  9. Brooks, P.C., Montgomery, A.M., Rosenfeld, M., Reisfeld, R.A., Hu, T., Klier, G., and Cheresh, D.A. (1994) Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels Cell 79, 1157–64.

    Article  PubMed  CAS  Google Scholar 

  10. Brandley, B.K., Swiedler, S.J., and Robbins, P.W. (1990) Carbohydrate ligands of the LEC cell adhesion molecules Cell 63, 861–3.

    Article  PubMed  CAS  Google Scholar 

  11. Lasky, L.A., Singer, M.S., Dowbenko, D., Imai, Y., Henzel, W.J., Grimley, C., Fennie, C., Gillett, N., Watson, S.R., and Rosen, S.D. (1992) An endothelial ligand for L-selectin is a novel mucin-like molecule Cell 69, 927–38.

    Article  PubMed  CAS  Google Scholar 

  12. Lasky, L.A. (1992) Selectins: interpreters of cell-specific carbohydrate information during inflammation Science 258, 964–9.

    Article  PubMed  CAS  Google Scholar 

  13. Phillips, M.L., Nudelman, E., Gaeta, F.C., Perez, M., Singhal, A.K., Hakomori, S., and Paulson, J.C. (1990) ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex Science 250, 1130–2.

    Article  PubMed  CAS  Google Scholar 

  14. Mulligan, M.S., Paulson, J.C., De Frees, S., Zheng, Z.L., Lowe, J.B., and Ward, P.A. (1993) Protective effects of oligosaccharides in P-selectin-dependent lung injury Nature 364, 149–51.

    Article  PubMed  CAS  Google Scholar 

  15. Weyrich, A.S., Ma, X.Y., Lefer, D.J., Albertine, K.H., and Lefer, A.M. (1993) In vivo neutralization of P-selectin protects feline heart and endothelium in myocardial ischemia and reperfusion injury J Clin Invest 91, 2620–9.

    Article  PubMed  CAS  Google Scholar 

  16. Hullinger, T., DeGraaf, G., Hartman, J., and Shebuski, R. (1995) The effect of P-selectin blockade on neointimal lesion development in a primate carotid injury model FASEB 9.

    Google Scholar 

  17. Taylor, M.E., and Drickamer, K. (2007) Paradigms for glycan-binding receptors in cell adhesion Curr Opin Cell Biol 19, 572–7.

    Article  PubMed  CAS  Google Scholar 

  18. Topol, E.J., Califf, R.M., Weisman, H.F., Ellis, S.G., Tcheng, J.E., Worley, S., Ivanhoe, R., George, B.S., Fintel, D., Weston, M., et al. (1994) Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. The EPIC investigators Lancet 343, 881–6.

    Article  PubMed  CAS  Google Scholar 

  19. Berlin, C., Berg, E.L., Briskin, M.J., Andrew, D.P., Kilshaw, P.J., Holzmann, B., Weissman, I.L., Hamann, A., and Butcher, E.C. (1993) Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1 Cell 74, 185–95.

    Article  PubMed  CAS  Google Scholar 

  20. Elices, M.J., Osborn, L., Takada, Y., Crouse, C., Luhowskyj, S., Hemler, M.E., and Lobb, R.R. (1990) VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site Cell 60, 577–84.

    Article  PubMed  CAS  Google Scholar 

  21. Issekutz, T.B. (1991) Inhibition of in vivo lymphocyte migration to inflammation and homing to lymphoid tissues by the TA-2 monoclonal antibody. A likely role for VLA-4 in vivo J Immunol 147, 4178–84.

    PubMed  CAS  Google Scholar 

  22. Hamann, A., Andrew, D.P., Jablonski-Westrich, D., Holzmann, B., and Butcher, E.C. (1994) Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo J Immunol 152, 3282–93.

    PubMed  CAS  Google Scholar 

  23. Springer, T.A. (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm Cell 76, 301–14.

    Article  PubMed  CAS  Google Scholar 

  24. Yednock, T.A., Cannon, C., Fritz, L.C., Sanchez-Madrid, F., Steinman, L., and Karin, N. (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin Nature 356, 63–6.

    Article  PubMed  CAS  Google Scholar 

  25. Cannella, B., and Raine, C.S. (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions Ann Neurol 37, 424–35.

    Article  PubMed  CAS  Google Scholar 

  26. Cerf-Bensussan, N., Jarry, A., Brousse, N., Lisowska-Grospierre, B., Guy-Grand, D., and Griscelli, C. (1987) A monoclonal antibody (HML-1) defining a novel membrane molecule present on human intestinal lymphocytes Eur J Immunol 17, 1279–85.

    Article  PubMed  CAS  Google Scholar 

  27. Kim, S., Bell, K., Mousa, S.A., and Varner, J.A. (2000) Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin Am J Pathol 156, 1345–62.

    Article  PubMed  CAS  Google Scholar 

  28. Cue, D., Southern, S.O., Southern, P.J., Prabhakar, J., Lorelli, W., Smallheer, J.M., Mousa, S.A., and Cleary, P.P. (2000) A nonpeptide integrin antagonist can inhibit epithelial cell ingestion of Streptococcus pyogenes by blocking formation of integrin alpha 5beta 1-fibronectin-M1 protein complexes Proc Natl Acad Sci USA 97, 2858–63.

    Article  PubMed  CAS  Google Scholar 

  29. The EPIC Investigators (1994) Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty N Engl J Med 330, 956–61.

    Google Scholar 

  30. Kleiman, N.S., Ohman, E.M., Califf, R.M., George, B.S., Kereiakes, D., Aguirre, F.V., Weisman, H., Schaible, T., and Topol, E.J. (1993) Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 Pilot Study J Am Coll Cardiol 22, 381–9.

    Article  PubMed  CAS  Google Scholar 

  31. Tcheng, J.E., Ellis, S.G., George, B.S., Kereiakes, D.J., Kleiman, N.S., Talley, J.D., Wang, A.L., Weisman, H.F., Califf, R.M., and Topol, E.J. (1994) Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty Circulation 90, 1757–64.

    Article  PubMed  CAS  Google Scholar 

  32. Tcheng, J.E., Harrington, R.A., Kottke-Marchant, K., Kleiman, N.S., Ellis, S.G., Kereiakes, D.J., Mick, M.J., Navetta, F.I., Smith, J.E., Worley, S.J., et al. (1995) Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker Integrelin in elective coronary intervention. IMPACT investigators Circulation 91, 2151–7.

    Article  PubMed  CAS  Google Scholar 

  33. Peerlinck, K., De Lepeleire, I., Goldberg, M., Farrell, D., Barrett, J., Hand, E., Panebianco, D., Deckmyn, H., Vermylen, J., and Arnout, J. (1993) MK-383 (L-700,462), a selective nonpeptide platelet glycoprotein IIb/IIIa antagonist, is active in man Circulation 88, 1512–7.

    Article  PubMed  CAS  Google Scholar 

  34. Cannon, C.P., McCabe, C.H., Borzak, S., Henry, T.D., Tischler, M.D., Mueller, H.S., Feldman, R., Palmeri, S.T., Ault, K., Hamilton, S.A., Rothman, J.M., Novotny, W.F., and Braunwald, E. (1998) Randomized trial of an oral platelet glycoprotein IIb/IIIa antagonist, sibrafiban, in patients after an acute coronary syndrome: results of the TIMI 12 trial. Thrombolysis in myocardial infarction Circulation 97, 340–9.

    Article  PubMed  CAS  Google Scholar 

  35. Muller, T.H., Weisenberger, H., Brickl, R., Narjes, H., Himmelsbach, F., and Krause, J. (1997) Profound and sustained inhibition of platelet aggregation by fradafiban, a nonpeptide platelet glycoprotein IIb/IIIa antagonist, and its orally active prodrug, lefradafiban, in men Circulation 96, 1130–8.

    Article  PubMed  CAS  Google Scholar 

  36. Simpfendorfer, C., Kottke-Marchant, K., Lowrie, M., Anders, R.J., Burns, D.M., Miller, D.P., Cove, C.S., DeFranco, A.C., Ellis, S.G., Moliterno, D.J., Raymond, R.E., Sutton, J.M., and Topol, E.J. (1997) First chronic platelet glycoprotein IIb/IIIa integrin blockade. A randomized, placebo-controlled pilot study of xemilofiban in unstable angina with percutaneous coronary interventions Circulation 96, 76–81.

    Article  PubMed  CAS  Google Scholar 

  37. Harrington, R.A., Armstrong, P.W., Graffagnino, C., Van De Werf, F., Kereiakes, D.J., Sigmon, K.N., Card, T., Joseph, D.M., Samuels, R., Granett, J., Chan, R., Califf, R.M., and Topol, E.J. (2000) Dose-finding, safety, and tolerability study of an oral platelet glycoprotein IIb/IIIa inhibitor, lotrafiban, in patients with coronary or cerebral atherosclerotic disease Circulation 102, 728–35.

    Article  PubMed  CAS  Google Scholar 

  38. Mousa, S., and Wityak, J. (1998) Orally active Isoxazoline GOIIb/IIIa antagonists Cardiovas Drug Rev 16, 48–61.

    Article  CAS  Google Scholar 

  39. Quinn, M., and Fitzgerald, D.J. (1998) Long-term administration of glycoprotein IIb/IIIa antagonists Am Heart J 135, S113–8.

    Article  Google Scholar 

  40. Vorchheimer, D.A., and Fuster, V. (1998) Oral platelet glycoprotein IIb/IIIa receptor antagonists: the present challenge is safety Circulation 97, 312–4.

    Article  PubMed  CAS  Google Scholar 

  41. Mousa, S.A., Bozarth, J.M., Edwards, S., Carroll, T., and Barrett, J. (1998) Novel technetium-99m-labeled platelet GPIIb/IIIa receptor antagonists as potential imaging agents for venous and arterial thrombosis Coron Artery Dis 9, 131–41.

    PubMed  CAS  Google Scholar 

  42. Srivatsa, S.S., Fitzpatrick, L.A., Tsao, P.W., Reilly, T.M., Holmes, D.R., Jr., Schwartz, R.S., and Mousa, S.A. (1997) Selective alpha v beta 3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: evidence for the functional importance of integrin alpha v beta 3 and osteopontin expression during neointima formation Cardiovasc Res 36, 408–28.

    Article  PubMed  CAS  Google Scholar 

  43. Liaw, L., Skinner, M.P., Raines, E.W., Ross, R., Cheresh, D.A., Schwartz, S.M., and Giachelli, C.M. (1995) The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro J Clin Invest 95, 713–24.

    Article  PubMed  CAS  Google Scholar 

  44. Yue, T.L., McKenna, P.J., Ohlstein, E.H., Farach-Carson, M.C., Butler, W.T., Johanson, K., McDevitt, P., Feuerstein, G.Z., and Stadel, J.M. (1994) Osteopontin-stimulated vascular smooth muscle cell migration is mediated by beta 3 integrin Exp Cell Res 214, 459–64.

    Article  PubMed  CAS  Google Scholar 

  45. van der Zee, R., Murohara, T., Passeri, J., Kearney, M., Cheresh, D.A., and Isner, J.M. (1998) Reduced intimal thickening following alpha(v)beta3 blockade is associated with smooth muscle cell apoptosis Cell Adhes Commun 6, 371–9.

    Article  PubMed  Google Scholar 

  46. Kerr, J.S., Slee, A.M., and Mousa, S.A. (2002) The alpha v integrin antagonists as novel anticancer agents: an update Expert Opin Investig Drugs 11, 1765–74.

    Article  PubMed  CAS  Google Scholar 

  47. Oba, M., Fukushima, S., Kanayama, N., Aoyagi, K., Nishiyama, N., Koyama, H., and Kataoka, K. (2007) Cyclic RGD peptide-conjugated polyplex micelles as a targetable gene delivery system directed to cells possessing alphavbeta3 and alphavbeta5 integrins Bioconjug Chem 18, 1415–23.

    Article  PubMed  CAS  Google Scholar 

  48. Flavin, T., Ivens, K., Rothlein, R., Faanes, R., Clayberger, C., Billingham, M., and Starnes, V.A. (1991) Monoclonal antibodies against intercellular adhesion molecule 1 prolong cardiac allograft survival in cynomolgus monkeys Transplant Proc 23, 533–4.

    PubMed  CAS  Google Scholar 

  49. Haug, C.E., Colvin, R.B., Delmonico, F.L., Auchincloss, H., Jr., Tolkoff-Rubin, N., Preffer, F.I., Rothlein, R., Norris, S., Scharschmidt, L., and Cosimi, A.B. (1993) A phase I trial of immunosuppression with anti-ICAM-1 (CD54) mAb in renal allograft recipients Transplantation 55, 766–72; Discussion 72–3.

    Article  PubMed  CAS  Google Scholar 

  50. Rosenblum, W.I., Nelson, G.H., Wormley, B., Werner, P., Wang, J., and Shih, C.C. (1996) Role of platelet-endothelial cell adhesion molecule (PECAM) in platelet adhesion/aggregation over injured but not denuded endothelium in vivo and ex vivo Stroke 27, 709–11.

    Article  PubMed  CAS  Google Scholar 

  51. Muller, W.A., and Randolph, G.J. (1999) Migration of leukocytes across endothelium and beyond: molecules involved in the transmigration and fate of monocytes J Leukoc Biol 66, 698–704.

    PubMed  CAS  Google Scholar 

  52. Gearing, A.J., and Newman, W. (1993) Circulating adhesion molecules in disease Immunol Today 14, 506–12.

    Article  PubMed  CAS  Google Scholar 

  53. Newman, W., Beall, L.D., Carson, C.W., Hunder, G.G., Graben, N., Randhawa, Z.I., Gopal, T.V., Wiener-Kronish, J., and Matthay, M.A. (1993) Soluble E-selectin is found in supernatants of activated endothelial cells and is elevated in the serum of patients with septic shock J Immunol 150, 644–54.

    PubMed  CAS  Google Scholar 

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  1. Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA

    Shaker A. Mousa

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  1. , Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sc, Discovery Drive One, Rensselaer, 12144, New York, USA

    Shaker A. Mousa

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Mousa, S.A. (2010). Adhesion Molecules: Potential Therapeutic and Diagnostic Implications. In: Mousa, S. (eds) Anticoagulants, Antiplatelets, and Thrombolytics. Methods in Molecular Biology, vol 663. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-803-4_11

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  • DOI: https://doi.org/10.1007/978-1-60761-803-4_11

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