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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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The activation of CD99 inhibits cell-extracellular matrix adhesion by suppressing β1 integrin affinity

  • Lee, Kyoung-Jin (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Lee, Sun-Hee (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Yadav, Birendra Kumar (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Ju, Hyun-Mi (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Kim, Min-Seo (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Park, Jeong-Hyun (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Jeoung, Doo-Il (Department of Biochemistry, Kangwon National University) ;
  • Lee, Han-Soo (Department of Biological Sciences, College of Natural Sciences, Kangwon National University) ;
  • Hahn, Jang-Hee (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University)
  • Received : 2011.09.19
  • Accepted : 2011.11.14
  • Published : 2012.03.31
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Abstract

CD99 is known to be involved in the regulation of cell-cell adhesion. However, it remains unclear whether CD99 controls cell-extracellular matrix adhesion. In this study, the effects of CD99 activation on cell-extracellular matrix adhesion were investigated. It was found that engagement of CD99 with the stimulating antibody YG32 downregulated the adhesion of MCF-7 cells to fibronectin, laminin and collagen IV in a dose-dependent manner. The CD99 effect on cell-ECM adhesion was inhibited by overexpression of the dominant negative form of CD99 or CD99 siRNA transfection. Treatment of cells with $Mn^{2+}$ or by ${\beta}_1$ integrin-stimulating antibody restored the inhibitory effect of CD99 on cell-ECM adhesion. Cross-linking CD99 inactivated ${\beta}_1$ integrin through conformational change. CD99 activation caused dephosphorylation at Tyr-397 in FAK, which was restored by the ${\beta}_1$ stimulating antibody. Taken together, these results provide the first evidence that CD99 inhibits cell-extracellular matrix adhesion by suppressing ${\beta}_1$ integrin affinity.

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References

  1. Sixt, M., Bauer, M., Lammermann, T. and Fassler, R. (2006) Beta1 integrins: zip codes and signaling relay for blood cells. Curr. Opin. Cell Biol. 18, 482-490. https://doi.org/10.1016/j.ceb.2006.08.007
  2. Al-Jamal, R. and Harrison, D. J. (2008) Beta1 integrin in tissue remodelling and repair: from phenomena to concepts. Pharmacol. Ther. 120, 81-101. https://doi.org/10.1016/j.pharmthera.2008.07.002
  3. Wang, X. Q. and Frazier, W. A. (1998) The thrombospondin receptor CD47 (IAP) modulates and associates with alpha2 beta1 integrin in vascular smooth muscle cells. Mol. Biol. Cell 9, 865-874. https://doi.org/10.1091/mbc.9.4.865
  4. Fenczik, C. A., Sethi, T., Ramos, J. W., Hughes, P. E. and Ginsberg, M. H. (1997) Complementation of dominant suppression implicates CD98 in integrin activation. Nature 390, 81-85. https://doi.org/10.1038/36349
  5. Kim, S. M. and Hahn, J. H. (2008) CD98 activation increases surface expression and clusteringof beta1 integrins in MCF-7 cells through FAK/Src- and cytoskeleton-independent mechanisms. Exp. Mol. Med. 40, 261-270. https://doi.org/10.3858/emm.2008.40.3.261
  6. Kotha, J., Longhurst, C., Appling, W. and Jennings, L. (2008) Tetraspanin CD9 regulates beta 1 integrin activation and enhances cell motility to fibronectin via a PI-3 kinase- dependent pathway. Exp. Cell Res. 314, 1811-1822. https://doi.org/10.1016/j.yexcr.2008.01.024
  7. Nishiuchi, R., Sanzen, N., Nada, S., Sumida, Y., Wada, Y., Okada, M., Takagi, J., Hasegawa, H. and Sekiguchi, K. (2005) Potentiation of the ligand-binding activity of integrin alpha3beta1 via association with tetraspanin CD151. PNAS 102, 1939-1944. https://doi.org/10.1073/pnas.0409493102
  8. Serru, V., Le Naour, F., Billard, M., Azorsa, D., Lanza, F., Boucheix, C. and Rubinstein, E. (1999) Selective tetraspan- integrin complexes (CD81/alpha4beta1, CD151/ alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions. Biochem. J. 340, 103-111. https://doi.org/10.1042/0264-6021:3400103
  9. Oinuma, I., Katoh, H. and Negishi, M. (2006) Semaphorin 4D/Plexin-B1-mediated R-Ras GAP activity inhibits cell migration by regulating beta(1) integrin activity. J. Cell Biol. 173, 601-613. https://doi.org/10.1083/jcb.200508204
  10. Oinuma, I., Ishikawa, Y., Katoh, H. and Negishi, M. (2004) The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. Science 305, 862-865. https://doi.org/10.1126/science.1097545
  11. Miao, H., Burnett, E., Kinch, M., Simon, E. and Wang, B. (2000) Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat. Cell Biol. 2, 62-69. https://doi.org/10.1038/35000008
  12. Levy, R., Dilley, J., Fox, R. and Warnke, R. (1979) A human thymus-leukemia antigen defined by hybridoma monoclonal antibodies. Proc. Natl. Acad. Sci. U.S.A. 76, 6552-6556. https://doi.org/10.1073/pnas.76.12.6552
  13. Hahn J. H., Choi, E. Y., Kim, S. H., Sohn, H. W., Ham, D. I., Chung, D. H., Kim, T. J., Lee, W. J., Park, C. K., Ree, H. J. and Park, S. H. (1997) CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion. J. Immunol. 159, 2250-2258.
  14. Schön, M., Arya, A., Murphy, E., Adams, C., Strauch, U., Agace, W., Marsal, J., Donohue, J., Her, H., Beier, D., Olson, S., Lefrancois, L., Brenner, M., Grusby, M. and Parker, C. (1999) Mucosal T lymphocyte numbers are selectively reduced in integrin alpha E (CD103)-deficient mice. J. Immunol. 162, 6641-6649.
  15. Schenkel, A., Mamdouh, Z., Chen, X., Liebman, R. and Muller, W. (2002) CD99 plays a major role in the migration of monocytes through endothelial junctions. Nat. Immunol. 2, 143-150. https://doi.org/10.1038/nri766
  16. Wingett, D., Forcier, K. and Nielson, C. (1999) A role for CD99 in T cell activation. Cell Immunol. 193, 17-23. https://doi.org/10.1006/cimm.1999.1470
  17. Pettersen, R., Bernard, G., Olafsen, M., Pourtein, M. and Lie, S. (2001) CD99 signals caspase-independent T cell death. J. Immunol. 166, 4931-4942. https://doi.org/10.4049/jimmunol.166.8.4931
  18. Sohn, H. W., Choi, E. Y., Kim, S. H., Lee, I., Chung, D. H., Sung, U., Hwang, D., Cho, S., Jun, B., Jang, J., Chi, J. and Park, S. H. (1998) Engagement of CD99 induces apoptosis through a calcineurin-independent pathway in Ewing's sarcoma cells. Am. J. Pathol. 153, 1937-1945. https://doi.org/10.1016/S0002-9440(10)65707-0
  19. Schenkel, A. R., Mamdouh, Z., Chen, X., Liebman, R. M. and Muller, W. A. (2002) CD99 plays a major role in the migration of monocytes through endothelial junctions. Nat. Immunol. 3, 143-150. https://doi.org/10.1038/ni749
  20. Dustin, M. L. and Springer, T. A. (1989) T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature 341, 619-624. https://doi.org/10.1038/341619a0
  21. Bernard, G., Raimondi, V., Alberti, I., Pourtein, M., Widjenes, J., Ticchioni, M. and Bernard, A. (2000) CD99 (E2) up-regulates alpha4beta1-dependent T cell adhesion to inflamed vascular endothelium under flow conditions. Eur. J. Immunol. 30, 3061-3065. https://doi.org/10.1002/1521-4141(200010)30:10<3061::AID-IMMU3061>3.0.CO;2-M
  22. Alberti, I., Bernard, G., Rouquette-Jazdanian, A. K., Pelassy, C., Pourtein, M., Aussel, C. and Bernard, A. (2002) CD99 isoforms expression dictates T cell functional outcomes. FASEB J. 16, 1946-1948. https://doi.org/10.1096/fj.02-0049fje
  23. Hahn, M. J., Yoon, S. S., Sohn, H. W., Song, H. G., Park, S. H. and Kim, T. J. (2000) Differential activation of MAP kinase family members triggered by CD99 engagement. FEBS Lett. 470, 350-354. https://doi.org/10.1016/S0014-5793(00)01330-2
  24. Ni, H., Li, A., Simonsen, N. and Wilkins, J. A. (1998) Integrin activation by dithiothreitol or Mn2+ induces a ligand- occupied conformation and exposure of a novel NH2-terminal regulatory site on the beta1 integrin chain. J. Biol. Chem. 273, 7981-7987. https://doi.org/10.1074/jbc.273.14.7981
  25. Dransfield, I. and Hogg, N. (1989) Regulated expression of Mg2+ binding epitope on leukocyte integrin alpha subunits. EMBO J. 8, 3759-3765.
  26. Mitra, S. K. and Schlaepfer, D. D. (2006) Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr. Opin. Cell. Biol. 18, 516-523. https://doi.org/10.1016/j.ceb.2006.08.011
  27. Lee, H. A., Park, I., Byun, H. J., Jeoung, D., Kim, Y. M. and Lee, H. (2011) Metastasis suppressor KAI1/CD82 attenuates the matrix adhesion of human prostate cancer cells by suppressing fibronectin expression and beta1 integrin activation. Cell. Physiol. Biochem. 27, 575-586. https://doi.org/10.1159/000329979
  28. Maione, F., Molla, F., Meda, C., Latini, R., Zentilin, L., Giacca, M., Seano, G., Serini, G., Bussolino, F. and Giraudo, E. (2009) Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models. J. Clin Invest 119, 3356-3372.
  29. Bourgin, C., Murai, K., Richter, M. and Pasquale, E. (2007) The EphA4 receptor regulates dendritic spine remodeling by affecting beta1-integrin signaling pathways. J. Cell. Biol. 178, 1295-1307. https://doi.org/10.1083/jcb.200610139
  30. Dail, M., Richter, M., Godement, P. and Pasquale, E. (2005) Eph receptors inactivate R-Ras through different mechanisms to achieve cell repulsion. J. Cell. Science 119, 1244-1254. https://doi.org/10.1242/jcs.02842
  31. Dufour, E. M., Deroche, A., Bae, Y. and Muller, W. A. (2008) CD99 is essential for leukocyte diapedesis in vivo. Cell. Commun. Adhes. 15, 351-363. https://doi.org/10.1080/15419060802442191
  32. Lou, O., Alcaide, P., Luscinskas, F. W. and Muller, W. A. (2007) CD99 is a key mediator of the transendothelial migration of neutrophils. J. Immunol. 178, 1136-1143. https://doi.org/10.4049/jimmunol.178.2.1136
  33. Imbert, A. M., Belaaloui, G., Bardin, F., Tonnelle, C., Lopez, M. and Chabannon, C. (2006) CD99 expressed on human mobilized peripheral blood CD34+ cells is involved in transendothelial migration. Blood 108, 2578-2586. https://doi.org/10.1182/blood-2005-12-010827
  34. Bixel, M. G., Li, H., Petri, B., Khandoga, A. G., Khandoga, A., Zarbock, A., Wolburg-Buchholz, K., Wolburg, H., Sorokin, L., Zeuschner, D., Maerz, S., Butz, S., Krombach, F. and Vestweber, D. (2010) CD99 and CD99L2 act at the same site as, but independently of, PECAM-1 during leukocyte diapedesis. Blood 116, 1172-1184. https://doi.org/10.1182/blood-2009-12-256388
  35. Bixel, M. G., Petri, B., Khandoga, A. G., Khandoga, A., Wolburg-Buchholz, K., Wolburg, H., Marz, S., Krombach, F. and Vestweber, D. (2007) A CD99-related antigen on endothelial cells mediates neutrophil but not lymphocyte extravasation in vivo. Blood 109, 5327-5336. https://doi.org/10.1182/blood-2006-08-043109
  36. Lee, K. J., Kim, H. A., Kim, P. H., Lee, H. S., Ma, K. R., Park, J. H., Kim, D. J. and Hahn, J. H. (2004) Ox-LDL suppresses PMA-induced MMP-9 expression and activity through CD36-mediated activation of PPAR-g. Exp. Mol. Med. 36, 534-544. https://doi.org/10.1038/emm.2004.68

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