Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer: prognostic value and analysis of their relationships.
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-2Ralpha) (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-2Ralpha (CD25) by preactivated T cells, we looked for a relationship between MMP-9 expression and soluble IL-2Ralpha 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-2Ralpha levels. These results led us to reassess the role of MMP-9 in the release of sIL-2Ralpha. Treatment of Kit225 leukaemic cells with recombinant MMP-9 slightly decreased membrane CD25 expression and was associated with an increased concentration of sIL-2Ralpha in the supernatants. However, using a selective inhibitor of MMP-9 we did not succeed in specifically inhibiting the release of sIL-2Ralpha by the Kit225 cell line or by phytohaemagglutinin (PHA)-activated peripheral blood mononuclear cells. In addition, in a preclinical mouse model, basal serum sIL-2Ralpha concentrations and sIL-2Ralpha 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-2Ralpha 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-2Ralpha, other proteases are involved in the shedding of sIL-2Ralpha. MMP-9 and sIL-2Ralpha appear therefore as independent prognostic markers in head and neck cancers.
El Houda Agueznay
N
N
EA 4054 Université Paris Descartes, Ecole Nationale Vétérinaire d'Alfort, Paris, France.
Badoual
C
C
Hans
S
S
Gey
A
A
Vingert
B
B
Peyrard
S
S
Quintin-Colonna
F
F
Ravel
P
P
Bruneval
P
P
Roncelin
S
S
Lelongt
B
B
Bertoglio
J
J
Fridman
W H
WH
Brasnu
D
D
Tartour
E
E
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000276:immunology; D002478:Cells, Cultured; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D008213:Lymphocyte Activation / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D053645:Interleukin-2 Receptor alpha Subunit; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D020780:Matrix Metalloproteinase 9