TY - JOUR
T1 - Soluble interleukin-2 receptor and metalloproteinase-9 expression in head and neck cancer
T2 - Prognostic value and analysis of their relationships
AU - El Houda Agueznay, N.
AU - Badoual, C.
AU - Hans, S.
AU - Gey, A.
AU - Vingert, B.
AU - Peyrard, S.
AU - Quintin-Colonna, F.
AU - Ravel, P.
AU - Bruneval, P.
AU - Roncelin, S.
AU - Lelongt, B.
AU - Bertoglio, J.
AU - Fridman, W. H.
AU - Brasnu, D.
AU - Tartour, E.
PY - 2007/1/1
Y1 - 2007/1/1
N2 - 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.
AB - 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.
KW - Cytokine
KW - Head and neck cancer
KW - MMP-9
KW - Prognostic marker
KW - Soluble IL-2 receptor
UR - http://www.scopus.com/inward/record.url?scp=34548534894&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2249.2007.03464.x
DO - 10.1111/j.1365-2249.2007.03464.x
M3 - Article
C2 - 17680822
AN - SCOPUS:34548534894
SN - 0009-9104
VL - 150
SP - 114
EP - 123
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 1
ER -