title: Matrix metalloproteinase-8 is overexpressed in Waldenström's macroglobulinemia cells, and specific inhibition of this metalloproteinase blocks release of soluble CD27.
abstract: Soluble CD27 (sCD27) is produced by Waldenström's macroglobulinemia (WM) cells, with high levels found in WM patients which may facilitate disease expansion. Matrix metalloproteinases (MMP) may facilitate sCD27 release by cleavage of CD27. By gene expression analysis, we observed significantly higher transcription levels of MMP-8 and MMP-9, with 58.5 and 16.7 fold increase in mean transcription levels in WM cells relative to healthy donor peripheral blood B cells (P = .04, and .05, respectively). We developed a model for study of sCD27 release by transfecting BCWM.1 WM cells and BL2126 lymphoblastic B cells, both of which express MMP-8 and MMP-9 with a vector expressing FLAG-tagged CD27 (pFLAG-CD27) which in the presence of phorbol myristate acetate resulted in ≥ 10-fold increase in sCD27 release. MMP inhibitors against MMP-8, but not MMP 2, 3, or 9 blocked release of sCD27. The results suggest that MMP-8 may play a role in the pathogenesis of WM, and that its inhibition may be of therapeutic value in WM.
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana Farber Cancer Institute, and Harvard Medical School, Boston, MA, USA.
authors.forename: Yangsheng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Lian
authors.initials: L
authors.lastname: Xu
authors.forename: Hsiuyi
authors.initials: H
authors.lastname: Tseng
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Jingrui
authors.initials: J
authors.lastname: Jiang
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Ciccarelli
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Patterson
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Hunter
authors.forename: Steven P
authors.initials: SP
authors.lastname: Treon
mesh_terms: D018941:Antigens, CD19 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D016000:Cluster Analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020784:Matrix Metalloproteinase 8 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000378:metabolism*; D008258:Waldenstrom Macroglobulinemia / Q000201:enzymology* / Q000235:genetics*
chemical_list: D018941:Antigens, CD19; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9