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Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer: prognostic value and analysis of their relationships

  1. N. El Houda Agueznay1,2,†,
  2. C. Badoual1,3,†,
  3. S. Hans4,
  4. A. Gey2,
  5. B. Vingert1,
  6. S. Peyrard5,
  7. F. Quintin-Colonna1,
  8. P. Ravel6,7,
  9. P. Bruneval3,
  10. S. Roncelin2,
  11. B. Lelongt8,
  12. J. Bertoglio9,
  13. W. H. Fridman2,
  14. D. Brasnu4,
  15. E. Tartour1,2

Article first published online: 3 AUG 2007

DOI: 10.1111/j.1365-2249.2007.03464.x

Issue

Clinical & Experimental Immunology

Clinical & Experimental Immunology

Volume 150, Issue 1, pages 114–123, October 2007

Additional Information

How to Cite

El Houda Agueznay, N., Badoual, C., Hans, S., Gey, A., Vingert, B., Peyrard, S., Quintin-Colonna, F., Ravel, P., Bruneval, P., Roncelin, S., Lelongt, B., Bertoglio, J., Fridman, W. H., Brasnu, D. and Tartour, E. (2007), Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer: prognostic value and analysis of their relationships. Clinical & Experimental Immunology, 150: 114–123. doi: 10.1111/j.1365-2249.2007.03464.x

Author Information

  1. 1

    EA 4054 Université Paris Descartes, Ecole Nationale Vétérinaire d'Alfort, Paris, France,

  2. 2

    Unité d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France,

  3. 3

    Unité d'Anatomie Pathologique, Hôpital Européen Georges Pompidou (HEGP), Paris, France,

  4. 4

    Department of Otorhinolaryngology-Head and Neck Surgery, HEGP, Paris, France,

  5. 5

    Centre d'Investigations Cliniques, Assistance Publique des Hopitaux de Paris, Paris, France,

  6. 6

    INSERM U254, Montpellier, France,

  7. 7

    Université Montpellier 1 et 2, CNRS, Centre de Biochimie Structurale, Montpellier, France,

  8. 8

    INSERM, U702, Hôpital Tenon AP-HP, Paris, France, and

  9. 9

    INSERM, U461, Faculté de Pharmacie Paris-XI, Chatenay-Malabry, France

  1. †

    These authors contributed equally to this study.

*Eric Tartour, Hôpital Européen Georges Pompidou, Unité d'Immunologie Biologique, 20 Rue Leblanc, 75908, Paris Cedex 15, France. E-mail: eric.tartour@egp.aphp.fr

Publication History

  1. Issue published online: 3 AUG 2007
  2. Article first published online: 3 AUG 2007
  3. Accepted for publication 14 June 2007

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Keywords:

  • cytokine;
  • head and neck cancer;
  • MMP-9;
  • prognostic marker;
  • soluble IL-2 receptor

Summary

In a series of 84 head and neck patients, a statistically significant correlation was observed between high serum soluble interleukin (IL)-2 receptor alpha (sIL-2Rα) (P = 0·034) and metalloproteinase-9 (MMP-9) concentrations (P = 0·036) at diagnosis and a shorter survival of these patients. As MMP-9 has been shown to mediate cleavage of IL-2Rα (CD25) by preactivated T cells, we looked for a relationship between MMP-9 expression and soluble IL-2Rα serum concentrations in these cancer patients. We did not find any correlation between intratumoral expression of MMP-9 or serum MMP-9 concentrations and serum sIL-2Rα levels. These results led us to reassess the role of MMP-9 in the release of sIL-2Rα. Treatment of Kit225 leukaemic cells with recombinant MMP-9 slightly decreased membrane CD25 expression and was associated with an increased concentration of sIL-2Rα in the supernatants. However, using a selective inhibitor of MMP-9 we did not succeed in specifically inhibiting the release of sIL-2Rα by the Kit225 cell line or by phytohaemagglutinin (PHA)-activated peripheral blood mononuclear cells. In addition, in a preclinical mouse model, basal serum sIL-2Rα concentrations and sIL-2Rα production by activated cells were not altered in MMP-9-deficient mice compared to wild-type mice. Interestingly, a broad spectrum metalloproteinase inhibitor inhibited the release of sIL-2Rα by PHA-activated peripheral blood mononuclear cells, suggesting that in contrast with current views concerning the major role of MMP-9 in the cleavage of membrane IL-2Rα, other proteases are involved in the shedding of sIL-2Rα. MMP-9 and sIL-2Rα appear therefore as independent prognostic markers in head and neck cancers.

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