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

Authors: El Houda Agueznay, N.; Badoual, C.; Hans, S.¹; Gey, A.²; Vingert, B.³; Peyrard, S.⁴; Quintin-Colonna, F.³; Ravel, P.; Bruneval, P.⁵; Roncelin, S.²; Lelongt, B.⁶; Bertoglio, J.⁷; Fridman, W. H.²; Brasnu, D.¹; Tartour, E.

Source: Clinical & Experimental Immunology, Volume 150, Number 1, October 2007 , pp. 114-123(10)

Publisher: Blackwell Publishing

Key:

- Free Content

- New Content

- Subscribed Content

- Free Trial Content

Abstract:

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.

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

Document Type: Research article

DOI: 10.1111/j.1365-2249.2007.03464.x

Affiliations: 1: Department of Otorhinolaryngology-Head and Neck Surgery, HEGP, Paris, France, 2: Unité d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France, 3: EA 4054 Université Paris Descartes, Ecole Nationale Vétérinaire d'Alfort, Paris, France, 4: Centre d'Investigations Cliniques, Assistance Publique des Hopitaux de Paris, Paris, France, 5: Unité d'Anatomie Pathologique, Hôpital Européen Georges Pompidou (HEGP), Paris, France, 6: INSERM, U702, Hôpital Tenon AP-HP, Paris, France, and 7: INSERM, U461, Faculté de Pharmacie Paris-XI, Chatenay-Malabry, France

You have access to the full text article on a website external to Ingentaconnect.

Please click here to view this article on InterScience.

You may be required to register and activate access on InterScience before you can obtain the full text. If you have any queries please contact onlinehelp@oxon.blackwellpublishing.com

Key:

- Free Content

- New Content

- Subscribed Content

- Free Trial Content

Share this item with others: These icons link to social bookmarking sites where readers can share and discover new web pages.