title: 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.
abstract: Regulatory molecules produced by stromal cells are often membrane bound until cleaved by matrix metalloproteinases (MMPs); cleavage can 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 < .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 = .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 < .001). 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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Mineo
authors.initials: M
authors.lastname: Iwata
authors.forename: Manoj
authors.initials: M
authors.lastname: Pillai
authors.forename: Aravind
authors.initials: A
authors.lastname: Ramakrishnan
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hackman
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Beverly
authors.initials: B
authors.lastname: Torok-Storb
mesh_terms: D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology*; D002478:Cells, Cultured / Q000378:metabolism; D018925:Chemokines / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D020780:Matrix Metalloproteinase 9