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Brief Report
Cell-surface MMP-9 regulates the invasive capacity of leukemia blast cells with monocytic features
Jenny Paupert, Veronique Mansat-De Mas, Cécile Demur, Bernard Salles and Catherine Muller
volume 7 | issue 8
15 April 2008Pages: 1049 - 1055
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The metalloprotease 9 (MMP-9), a known mediator of tumour invasion, is secreted as a 92kDa pro-form but a non-secreted variant of 85 Kda has been described. The importance of this variant pro-form in tumour progression remains poorly defined. We previously showed that the DNA repair protein Ku interacts at the cell surface of leukaemia cell lines with the 85 Kda pro-form of MMP-9 and these Ku/MMP-9 complexes regulates cell invasion, highlighting their importance in haematological malignancies. We demonstrate here that all samples of acute myeloid leukaemia (AML) blasts purified from bone marrow of 16 affected patients express the 85 Kda form of MMP-9. However, only AML that display monocytic lineage markers (AML4/5) express this form at the cell surface with co-expression of the membrane associated form of Ku. Blocking antibodies directed against Ku or MMP-9 specifically inhibited cell invasion of those expressing Ku/MMP-9 on the cell surface. The membrane form of Ku might represent an important factor in the exposition to the cell surface of this specific MMP-9 pro-form in AML with monocytic features. These results might have important functional significance in the occurrence of extra-medullar infiltrates of leukaemia cells that occurs frequently during the onset of monocyte-related AML sub-types.
Authors
Jenny Paupert
Université toulouse III/CNRS UMR 5089; Toulouse, France
Veronique Mansat-De Mas
CHU Purpan; Toulouse, France
Cécile Demur
CHU Purpan; Toulouse, France
Bernard Salles
Université toulouse III/CNRS UMR 5089; Toulouse, France
Catherine Muller
Université toulouse III/CNRS UMR 5089; Toulouse, France