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Blood, 1 January 2007, Vol. 109, No. 1, pp. 85-92. Prepublished online as a Blood First Edition Paper on September 5, 2006; DOI 10.1182/blood-2006-05-020289.
Submitted May 12, 2006
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA * 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.
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