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Cell Adhesion Molecules: Potential Therapeutic & Diagnostic Implications

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Abstract

The role of cell adhesion molecules (CAM) and extracellular matrix proteins (ECM) in various pathological processes including angiogenesis, thrombosis, apoptosis, cell migration & proliferation are 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 is evident from the potential role of the platelet GPIIb/IIIa integrin in the prevention and diagnosis of various thromboembolic disorders. Additionally, the use of soluble adhesion molecules as potential diagnostic markers for acute and chronic leukocyte, platelet, and endothelial cellular insult are increasingly utilized. The development of various therapeutic and diagnostic candidates based on the key role of CAM, with special emphasis on integrins in various diseases as well as the structure-function aspects of cell adhesion and signaling of the different CAM and ECM are highlighted.

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References

  1. Cox, D., Aoki, T., Seki, J., Motoyama, Y., & Yoshida, K. (1994). The pharmacology of the integrins. Medicinal Research Reviews, 14(2), 195–228.

    Article  PubMed  CAS  Google Scholar 

  2. Albelda, S. M., & Buck, C. A. (1990). Integrins and other cell adhesion molecules. The FASEB Journal, 4, 2868–2880.

    PubMed  CAS  Google Scholar 

  3. Cook, N. S., Kottirsch, G., & Zerwes, H. (1994). Platelet glycoprotein IIb/IIIa antagonists. Drugs Future, 19(2), 135–159.

    Google Scholar 

  4. Gold, H., Gimple, L. W., & Yasuda, T., et al. (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. The Journal of Clinical Investigation, 86, 651–659.

    PubMed  CAS  Google Scholar 

  5. Mousa, S. A., & Ahmad, S. (2007). Platelet GPIIb/IIIa antagonist, XV459, in heparin-induced thrombocytopenia. American Journal of Hematology, 82(4), 276–282.

    Article  PubMed  CAS  Google Scholar 

  6. Mousa, S. A., Bozarth, J. M., & Forsythe, M. S., et al. (1993). Anti-platelet efficacy and specificity of DMP 728, a novel platelet GPIIb/IIIa receptor antagonist. Cardiology, 83, 374–382.

    Article  PubMed  CAS  Google Scholar 

  7. Mousa, S. A., Bozarth, J. M., & Forsythe, M. S., et al. (1994). Antiplatelet and antithrombotic efficacy of DMP 728, a novel platelet GPIIb/IIIa receptor antagonist. Circulation, 89(1), 3–12.

    PubMed  CAS  Google Scholar 

  8. Mousa, S. A., & Topol, E. (1997). Novel antiplatelet therapies: Recent advances. In Patrick, W., Serruys, & David Holmes (Ed.), The development of platelet GPIIb/IIIa receptor antagonists. Current Review of Interventional Cardiology (3rd ed., vol. 13, pp. 114–129). Philadelphia, PA: Current Medicine.

  9. Brooks, P. C., Clark, R. A. F., & Cheresh, D. A. (1994). Requirement of vascular integrin αvβ3 for angiogenesis. Science, 264, 569–571.

    Google Scholar 

  10. Brooks, P. C., Montgomery, A. M. P., & Rosenfield, M., et al. (1994). Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell, 79, 1157–1164.

    Article  PubMed  CAS  Google Scholar 

  11. Brandley, B, Swiedler, S., & Rabbins, P. (1990). Carbohydrate ligands for the LEC cell adhesion molecules. Cell, 63, 861–863.

    Article  PubMed  CAS  Google Scholar 

  12. Lasky, L. A., Singer, M., & Dowbenko, D., et al. (1992). An endothelial ligand for L-selectin is a novel mucin-like molecule. Cell, 69, 927–938.

    Article  PubMed  CAS  Google Scholar 

  13. Lasky, L. A. (1992). Selectins: Interproteins of cell-specific carboyhdrate information during inflammation. Science, 258, 964–968.

    Article  PubMed  CAS  Google Scholar 

  14. Phillips, M. L., Nudelman, E., & Gaeta, F. A., et al. (1990). ELAM-1 mediate cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science, 250, 1130–1132.

    Article  PubMed  CAS  Google Scholar 

  15. Weyrich, A. S., Ma, X.-L., Leter, D. J., Albertine, K. H., & Lefer, A. M. (1993). In vivo neutralization of P-selectin protects Feline heart and endothelium in myocardial ischemia and reperfusion injury. The Journal of Clinical Investigation, 91, 2620–2629.

    PubMed  CAS  Google Scholar 

  16. Mulligan, M. S., Paulson, J. C., & De Frees, S., et al. (1993). Protective effects of oligo-saccharides in P-selectin -dependent lung injury. Nature, 364, 149–151.

    Article  PubMed  CAS  Google Scholar 

  17. Hullinger, T. G., De Graaf, G. L., Hartman, J. C., & Shebuski, R. J. (1995). The effect of P-selectin blockade on neointimal lesion development in a primate carotid injury model. FASEB, 9, 4897.

    Google Scholar 

  18. Paulson, J. C. (1992). Selectin/carbohydrate-mediated adhesion of leukocytes. In J. M. Harlan, & D. Y. Liu (Ed.), Adhesion: Its role in inflammatory disease. Chapter 2 (pp. 19–42). W.H. Freeman and Company.

  19. Topol, E. J., Califf, R. M., & Weisman, H. F., et al. (1994). Randomized trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. Lancet, 343, 881–886.

    Article  PubMed  CAS  Google Scholar 

  20. Hamann, A., Andrew, D. P., Jablonski-Westrich, D., Holzmann, B., & Butcher, E. C. (1994). Role of α4-integrins in lymphocyte homing to mucosal tissues in vivo. Journal of Immunology, 152, 3282–3293.

    CAS  Google Scholar 

  21. Issekutz, T. B. (1991). Inhibition of in vivo lymphocyte migration to inflammation and homing to lymphoid tissues by TA-2 monoclonal antibody. Journal of Immunology, 147, 4178–4184.

    CAS  Google Scholar 

  22. Elices, M. J., Osborn, L., & Takada, Y., et al. (1990). VCAM-1 on activated endothelium interacts with leukocyte integrin VLA-4 at asite distinct from the VLA-4/fibronectin binding site. Cell, 60, 577–578.

    Article  PubMed  CAS  Google Scholar 

  23. Berlin, C., Berg, E. L., Briskin, M. J., & Andrew, D. P., et al. (1994). α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell, 74, 185–195.

    Article  Google Scholar 

  24. Yednock, T. A., Cannon, C., Fritz, L. C., Sanchez-Madrid, F., Steinman, L., & Karin, N. (1992). Prevention of experimental autoimmune encephalomyelitis by antibodies against α4β1 integrin. Nature, 356, 63–66.

    Article  PubMed  CAS  Google Scholar 

  25. Springer, T. A. (1994). Traffic signals for lymphocyte recirculation and leukocyte emigration. The multistep paradigm. Cell, 76, 301–314.

    Article  PubMed  CAS  Google Scholar 

  26. Cannella, B., & Raine, C. S. (1995). The adhesion molecule and cytokine profile of multiple sclerosis lesions. Annals of Neurology, 37, 424–435.

    Article  PubMed  CAS  Google Scholar 

  27. Cerf-Bensussan, N., Jarry, A., & Lisowska-Grospierre, B., et al. (1987). A monoclonal (HML-1) defining a novel membrane molecule present on human intestinal lymphocytes. European Journal of Immunology, 17, 1279–1285.

    Article  PubMed  CAS  Google Scholar 

  28. Varner, J., Mousa, S. A. (1998). Antagonists of vascular cell integrin α5β1 inhibit angiogenesis. Circulation, 98(Suppl. I), I-795, 4166.

  29. Cue D, Southern, S., Southern, P., Jadhav, P. K., Lorelli, W., Smallheer, J., Mousa, S., & Cleary, P. (2000). A nonpeptide integrin antagonist can inhibit epithelial cell ingestion of streptococcus pyogenes by blocking formation of integrin α5β1 –fibronectin –M1 protein complex. Proceedings of the National Academy of Sciences, 97(6), 2858–2863.

    Article  CAS  Google Scholar 

  30. Figdor, C. G., & Kooyk, Y. V. (1992). Regulation of cell adhesion. In J. M. Harlan, & D. Y. Liu (Ed.), Chapter 7 (pp. 151–182). W.H. Freeman and Company.

  31. Tcheng, J. E., Ellis, S. G., & George, B. S., et al. (1994). Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty. Circulation, 90, 1757–1764.

    PubMed  CAS  Google Scholar 

  32. EPIC Investigators. (1994). Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The New England Journal of Medicine, 330, 956–961.

    Article  Google Scholar 

  33. Kleiman, N. S., Ohman, E., & Califf, R. M., et al. (1993). Profound inhibition of platelet aggregation with monoclonal antibody 73E Fab after thrombolytic therapy: Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 Pilot Study. Journal of the American College of Cardiology, 22, 381–9.

    Article  PubMed  CAS  Google Scholar 

  34. Tcheng, J. E., Harrington, R. A., & Kottke-Marchant K., et al. (1995). Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker, Integrilin in elective coronary intervention. IMPACT Investigators. Circulation, 91(8), 215–217.

    Google Scholar 

  35. Peerlinck, K., De Lepeleire, I., & Goldberg, M., et al. (1993). MK383 (L-700462), a selective nonpeptide platelet glycoprotein IIb/IIIa antagonist, is active in man. Circulation, 88(4 pt 1), 1512–1517.

    PubMed  CAS  Google Scholar 

  36. Théroux, P., Kouz, S., & Knudtson, M. L., et al. (1994). A randomized double-blind controlled trial with the non-peptide platelet GPIIb/IIIa antagonist RO 44–9883 in unstable angina [abstract]. Circulation, 90, 1–232.

    Google Scholar 

  37. Kottke-Marchant, K., Simpfendorfer, C., Lowrie, M., Burns, D., & Anders, R. J. (1995). Sustained but variable inhibition of platelet aggregation with Xemilofiban, an oral GPIIb/IIIa receptor antagonist, in patients with unstable angina. Circulation, 92(8 Suppl.), I-488.

    Google Scholar 

  38. Muller, T. H., Weisenberger, H., Brickl, R., Narjes, H., Himmelsbach, F., & Krause, J (1997). Profound and sustained inhibition of platelet aggregation by Fradafiban, nonpeptide platelet glycoprotein IIb/IIIa antagonist, and its orally active prodrug, Lefradafiban, in men. Circulation, 96(4), 1130–1138.

    PubMed  CAS  Google Scholar 

  39. Cannon, C. P., McCabe, C. H., Borzak, S., Henry, T. D., Tischler, M. D., Mueller, H. S., Feldman, R., & Palmeri, S. T., et al. (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(4), 340–349.

    PubMed  CAS  Google Scholar 

  40. Mousa, S. A., & Wityak, J. (1998). Orally active Isoxazoline GPIIb/IIIa antagonists. Cardiovascular Drug Reviews, 16(1), 48–61.

    Article  CAS  Google Scholar 

  41. Harrington, R. A., Graffagnino, C., Armstrong, P. W., Joseph, D., & Card, T. L., et al. (1998). Dose-finding and tolerability of a new oral platelet GPIIb/IIIa inhibitor, SB 214857, in patients with coronary artery and cerebrovascular disease: The APLAUD results. Circulation, 98(17 suppl.), I-251, P 1303.

  42. Vorchheimer, D. A., & Fuster, V. (1998). Oral platelet glycoprotein IIb/IIIa receptor antagonists: the present challenge is safety [editorial; comment]. Circulation, 97(4), 312–314.

    PubMed  CAS  Google Scholar 

  43. Quinn, M., & Fitzgerald, D. J. (1998). Long-term administration of glycoprotein IIb/IIIa antagonists. American Heart Journal, 135(5 Pt 2 Su), S113–S118.

    Article  PubMed  CAS  Google Scholar 

  44. Mousa, S., Bozarth, J., Edward, S., Carroll, T., & Barrett, J. (1998). Novel Technetium-99m Labelled Platelet GPIIb/IIIa Receptor Antagonists For Imaging Venous & Arterial Thrombosis. Coronary Artery Disease, 9(2/3), 1–11.

    Google Scholar 

  45. Srivasata, S., Reilly, T., Shwartz, R., Holmes, D., & Mousa, S. (1996). Selective αvβ3 integrin blockade limits neointima hyperplasia and lumen stenosis in stented porcine coronary artery injury in Pig. Circulation, 94(8), I-41, 0231 (abst.).

    Google Scholar 

  46. Yue, T.-L., McKenna, P. J., & Ohlstein, E. H., et al. (1994). Osteopontin-stimulated vascular smooth muscle cell migration is mediated by β3 integrin. Experimental Cell Research, 214, 459–464.

    Article  PubMed  CAS  Google Scholar 

  47. Liaw, L., Skiner, M. P., & Raines, E. W., et al. (1995). The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. The Journal of Clinical Investigation, 95, 713–724.

    Article  PubMed  CAS  Google Scholar 

  48. Zee, R., Passeri, J., Barry, J., Cheresh, D., & Isner, J. (1996). A neutralizing antibody to the alpha v Beta 3 integrin reduces neointimal thickening in a balloon-injured iliac artery. Circulation, 94(8), 1505 (abst.).

    Google Scholar 

  49. Flavin, T., Rothlein, R., Faanes, R., Ivens, K., & Starnes, V. A. (1991). Monoclonal antibody against intercellular adhesion molecule (ICAM)-1 prolongs cardiac allograft survival in cynomologus monkey. Transplantation Proceedings, 23, 533–534.

    PubMed  CAS  Google Scholar 

  50. Haug, C. E., Colvin, R. B., & Delmonico, F. L., et al. (1993). A phase I trial of immunosuppressant with anti-ICAM-1 (CD54) mAb in renal allograft recipient. Transplantation, 55(4), 766–773.

    Article  PubMed  CAS  Google Scholar 

  51. Rosenblum, W. I., Nelson, G. H., Wormley, B., Werner, P., Wang, J., & Shih, C.Y. (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, 709–711.

    PubMed  CAS  Google Scholar 

  52. Yamazald, T., Seko, Y., & Tamatani, T., et al. (1993). Expression of intracellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size with antibodies against cell adhesion molecules. The American Journal of Pathology, 143, 410–418.

    Google Scholar 

  53. Simpson, P. J., Todd, R. F., & Micelson, J. K., et al. (1990). sustained limitation of myocardial reperfusion injury by a monoclonal antibody that alter leukocyte function. Circulation, 81, 226–237.

    PubMed  CAS  Google Scholar 

  54. Newman, W., Dawson, B. L., & Carson, C. W., et al. (1993). Soluble E-selectins is found in supernatants of activated endothelial cells and is elevated in serum of patients with septic shock. Journal of Immunology, 150, 644–654.

    CAS  Google Scholar 

  55. Gearing, A. J. H., & Newman, W. (1993). Circulating adhesion molecules in disease. Immunology Today, 14(10), 506–512.

    Article  PubMed  CAS  Google Scholar 

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  1. The Pharmaceutical research Institute, Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY, USA

    Shaker A. Mousa

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Mousa, S.A. Cell Adhesion Molecules: Potential Therapeutic & Diagnostic Implications. Mol Biotechnol 38, 33–40 (2008). https://doi.org/10.1007/s12033-007-0072-7

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