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

Oncogene. 2002 Aug 8;21(34):5213-23. doi: 10.1038/sj.onc.1205684.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Adhesion
  • Collagen Type IV / metabolism
  • Cytotoxicity, Immunologic / immunology*
  • DNA Primers / chemistry
  • Drug Resistance, Neoplasm
  • Gelatin / metabolism
  • HL-60 Cells / immunology*
  • HL-60 Cells / metabolism*
  • Humans
  • Immunity, Cellular
  • In Vitro Techniques
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Killer Cells, Natural / immunology*
  • Leukemia, Promyelocytic, Acute / immunology
  • Matrix Metalloproteinase 9 / physiology*
  • Mutation
  • Polymerase Chain Reaction
  • Precipitin Tests
  • Transfection
  • Tumor Cells, Cultured / immunology


  • Collagen Type IV
  • DNA Primers
  • Intercellular Adhesion Molecule-1
  • Gelatin
  • Matrix Metalloproteinase 9