Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Matrix metalloproteinase 9 (MMP-9/gelatinase B) proteolytically cleaves ICAM-1 and participates in tumor cell resistance to natural killer cell-mediated cytotoxicity

Oncogene volume 21, pages 5213–5223 (2002)Cite this article

Abstract

Shedding of intercellular adhesion molecule 1 (ICAM-1) is believed to play a role in tumor cell resistance to cell-mediated cytotoxicity. However, the mechanism whereby ICAM-1 is shed from the surface of tumor cells remains unclear. In this study, we have addressed the possibility that matrix metalloproteinases are implicated in ICAM-1 shedding. Our observations suggest a functional relationship between ICAM-1 and matrix metalloproteinase 9 (MMP-9) whereby ICAM-1 provides a cell surface docking mechanism for proMMP-9, which, upon activation, proteolytically cleaves the extracellular domain of ICAM-1 leading to its release from the cell surface. MMP-9-dependent shedding of ICAM-1 is found to augment tumor cell resistance to natural killer (NK) cell-mediated cytotoxicity. Taken together, our observations propose a mechanism for ICAM-1 shedding from the cell surface and provide support for MMP involvement in tumor cell evasion of immune surveillance.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Altomonte M, Gloghini A, Bertola G, Gasparollo A, Carbone A, Ferrone S, Maio M . 1993 Cancer Res. 53: 3343–3348

  • Aoudjit F, Potworowski EF, St-Pierre Y . 1998 J. Immunol. 160: 2967–2973

  • Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B . 1990 Cell 61: 1303–1313

  • Becker JC, Brocker EB . 1995 Recent Results Cancer Res. 139: 205–214

  • Becker JC, Dummer R, Hartmann AA, Burg G, Schmidt RE . 1991 J. Immunol. 147: 4398–4401

  • Bergers G, Coussens LM . 2000 Curr. Opin. Genet. Dev. 10: 120–127

  • Bernhard EJ, Gruber SB, Muschel RJ . 1994 Proc. Natl. Acad. Sci. USA 91: 4293–4297

  • Bernhard EJ, Muschel RJ, Hughes EN . 1990 Cancer Res. 50: 3872–3877

  • Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA . 1993 Crit. Rev. Oral Biol. Med. 4: 197–250

  • Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP, Cheresh DA . 1996 Cell 85: 683–693

  • Fonsatti E, Altomonte M, Coral S, Cattarossi I, Nicotra MR, Gasparollo A, Natali PG, Maio M . 1997 Br. J. Cancer 76: 1255–1261

  • Gong JH, Maki G, Klingemann HG . 1994 Leukemia 8: 652–658

  • Grothey A, Heistermann P, Philippou S, Voigtmann R . 1998 Br. J. Cancer 77: 801–807

  • Gu B, Bendall LJ, Wiley JS . 1998 Blood 92: 946–951

  • Guo H, Li R, Zucker S, Toole BP . 2000 Cancer Res. 60: 888–891

  • Hafezi-Moghadam A, Thomas KL, Prorock AJ, Huo Y, Ley K . 2001 J. Exp. Med. 193: 863–872

  • Harning R, Mainolfi E, Bystryn JC, Henn M, Merluzzi VJ, Rothlein R . 1991 Cancer Res. 51: 5003–5005

  • Herron GS, Banda MJ, Clark EJ, Gavrilovic J, Werb Z . 1986 J. Biol. Chem. 261: 2814–2818

  • Hotary K, Allen E, Punturieri A, Yana I, Weiss SJ . 2000 J. Cell. Biol. 149: 1309–1323

  • Huang HY, Wen Y, Irwin JC, Kruessel JS, Soong YK, Polan ML . 1998 J. Clin. Endocrinol. Metab. 83: 1721–1729

  • Hynes RO, Lander AD . 1992 Cell 68: 303–322

  • Ismair MG, Ries C, Lottspeich F, Zang C, Kolb HJ, Petrides PE . 1998 Leukemia 12: 1136–1143

  • Kleiner DE, Stetler-Stevenson WG . 1999 Cancer Chemother. Pharmacol. 43: Suppl S42–S51

  • Kondapaka SB, Fridman R, Reddy KB . 1997 Int. J. Cancer 70: 722–726

  • Kridel SJ, Chen E, Kotra LP, Howard EW, Mobashery S, Smith JW . 2001 J. Biol. Chem. 276: 20572–20578

  • Lyons PD, Benveniste EN . 1998 Glia 22: 103–112

  • Makgoba MW, Sanders ME, Ginther Luce GE, Dustin ML, Springer TA, Clark EA, Mannoni P, Shaw S . 1988 Nature 331: 86–88

  • Mazzieri R, Masiero L, Zanetta L, Monea S, Onisto M, Garbisa S, Mignatti P . 1997 EMBO J. 16: 2319–2332

  • Mitsiades N, Poulaki V, Tseleni-Balafouta S, Koutras DA, Stamenkovic I . 2000 Cancer Res. 60: 4122–4129

  • Nagase H, Woessner Jr JF . 1999 J. Biol. Chem. 274: 21491–21494

  • Okamoto I, Kawano Y, Tsuiki H, Sasaki J, Nakao M, Matsumoto M, Suga M, Ando M, Nakajima M, Saya H . 1999 Oncogene 18: 1435–1446

  • Olson MW, Toth M, Gervasi DC, Sado Y, Ninomiya Y, Fridman R . 1998 J. Biol. Chem. 273: 10672–10681

  • Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G . 1998 Nature 392: 190–193

  • Peschon JJ, Slack JL, Reddy P, Stocking KL, Sunnarborg SW, Lee DC, Russell WE, Castner BJ, Johnson RS, Fitzner JN, Boyce RW, Nelson N, Kozlosky CJ, Wolfson MF, Rauch CT, Cerretti DP, Paxton RJ, March CJ, Black RA . 1998 Science 282: 1281–1284

  • Pizzolo G, Vinante F, Nadali G, Ricetti MM, Morosato L, Marrocchella R, Vincenzi C, Semenzato G, Chilosi M . 1993 Br. J. Haematol. 84: 161–162

  • Sanchez-Rovira P, Jimenez E, Carracedo J, Barneto IC, Ramirez R, Aranda E . 1998 Eur. J. Cancer 34: 394–398

  • Shapiro SD . 1998 Curr. Opin. Cell Biol. 10: 602–608

  • Springer TA . 1990 Annu. Rev. Cell Biol. 6: 359–402

  • Springer TA . 1994 Cell 76: 301–314

  • Stamenkovic I . 2000 Semin. Cancer Biol. 10: 415–433

  • Stamenkovic I, Seed B . 1990 Nature 345: 74–77

  • Tam YK, Maki G, Miyagawa B, Hennemann B, Tonn T, Klingemann HG . 1999 Hum. Gene Ther. 10: 1359–1373

  • Toth M, Gervasi DC, Fridman R . 1997 Cancer Res. 57: 3159–3167

  • Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, Shapiro SD, Senior RM, Werb Z . 1998 Cell 93: 411–422

  • Werb Z . 1997 Cell 91: 439–442

  • Yu Q, Stamenkovic I . 1999 Genes Dev. 13: 35–48

  • Yu Q, Stamenkovic I . 2000 Genes Dev. 14: 163–176

  • Yu WH, Woessner Jr JF . 2000 J. Biol. Chem. 275: 4183–4191

  • Zhao L, Shey M, Farnsworth M, Dailey MO . 2001 J. Biol. Chem. 276: 30631–30640

Download references

Author information

Authors and Affiliations

  1. Molecular Pathology Unit and MGH Cancer Center, Massachusetts General Hospital, Boston, 02129, Massachusetts, MA, USA

    Emilio Fiore, Carlo Fusco & Ivan Stamenkovic

  2. Institut Universitaire de Pathologie, 25 Rue du Bugnon, CH-1011, Lausanne, Switzerland

    Ivan Stamenkovic

  3. Ludwig Institute for Cancer Research, Lausanne Branch, Chemin des Boveresses 155, CH-1066, Epalinges, Switzerland

    Pedro Romero

Authors
  1. Emilio Fiore
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlo Fusco
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pedro Romero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ivan Stamenkovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ivan Stamenkovic.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fiore, E., Fusco, C., Romero, P. et al. Matrix metalloproteinase 9 (MMP-9/gelatinase B) proteolytically cleaves ICAM-1 and participates in tumor cell resistance to natural killer cell-mediated cytotoxicity. Oncogene 21, 5213–5223 (2002). https://doi.org/10.1038/sj.onc.1205684

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205684

Keywords

This article is cited by

Search

Advanced search

Quick links