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. (Blood. 2007;109: [85][86][87][88][89][90][91][92]

Phosphorylation of FOXP3 by LCK Downregulates MMP9 Expression and Represses Cell Invasion

“…cDNAs were mixed with a QuantiTect TM SYBR Green PCR Master Mix (Qiagen) and the following primers. Forward and reverse oligonucleotide primers were 5′-GGGCTTAGATCATTCCTCAGTGCC-3′ and 5′-GAAGATGTTCACGTTGCAGGCATC-3′ for MMP9 [25]; and 5′-CGGGAAGCTTGTCATCAATGG-3′ and 5′-GGCAGTGATGGCATGGACTG-3′ for GAPDH. Real-time PCR was performed using CHROMO 4 TM Continuous Fluorescence Detector (Bio-Rad).…”

Targeting of the bone marrow microenvironment improves outcome in a murine model of myelodysplastic syndrome

“…1 In vitro stromal abnormalities in MDS [2][3][4][5][6][7][8][9][10][11] have suggested the possibility that the bone marrow microenvironment (BMME) may contribute to disease progression and may therefore be a valuable therapeutic target. However, the lack of examination of the BMME in a robust in vivo model of MDS has limited progress in understanding the reciprocal interactions between abnormal MDS hematopoietic cells and the BMME.…”

Biology of BM failure syndromes: role of microenvironment and niches

“…61 MDS stromal cells induce altered matrix metalloproteinase expression in clonally-derived monocytes but the significance of this finding is unclear. 62 Expression of adhesion molecules including CD166 and CD29 was altered in MDS-derived mesenchymal stromal cells; however, it is not clear if these abnormalities influence the pathogenesis of MDS. 49 …”