Submitted May 12, 2006
Accepted August 12, 2006
Reduced expression of inducible gelatinase B/matrix metalloproteinase-9 in monocytes from patients with myelodysplastic syndrome: Correlation of inducible levels with the percentage of cytogenetically-marked cells and with marrow cellularity
Mineo Iwata, Manoj Pillai, Aravind Ramakrishnan, Robert C. Hackman, H Joachim Deeg, Ghislain M.M. Opdenakker, and Beverly S Torok-Storb*
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA
Laboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, Belgium
* Corresponding author; email: btorokst{at}fhcrc.org.
Regulatory molecules produced by stromal cells are often membrane-bound until cleaved by matrix metalloproteinases (MMP); cleavage can serve to either activate or inactivate regulatory functions. We report here that marrow stromal cells induce the expression of MMP-9 in monocytes. Induction was contact independent and could be reproduced with recombinant MCP-1/CCL2, whereas IL-6, M-CSF, G-CSF, GM CSF, IL-8/CXCL8, SDF-1/CXCL12, and MGSA/CXCL1 did not have this effect. Stroma-induced levels of MMP-9 in the monocyte population from healthy donors were relatively consistent, whereas induced levels varied significantly (P<0.001) in the CD14+ population from 27 patients with myelodysplastic syndrome (MDS). In patients with a clonal chromosomal marker, the level of inducible MMP-9 expression in the monocyte population was inversely correlated with the percentage of marker-positive cells (n=11, P=0.01), suggesting that the ability to induce MMP-9 may be compromised in clonally-derived monocytes. The inducible levels of MMP-9 were also inversely correlated with marrow cellularity observed in biopsies from MDS patients (P=0.0006). We conclude that monocytes can express MMP-9 in response to stromal factors and that this response may be significantly decreased in MDS-derived monocytes.
