title: Extracellular matrix remodeling by bone marrow fibroblast-like cells correlates with disease progression in multiple myeloma.
abstract: The pathogenesis of multiple myeloma (MM) is regarded as a multistep process, in which an asymptomatic stage of monoclonal gammopathy of undetermined significance (MGUS) precedes virtually all cases of MM. Molecular events characteristic for the transition from MGUS to MM are still poorly defined. We hypothesized that fibroblast-like cells in the tumor microenvironment are critically involved in the pathogenesis of MM. Therefore, we performed a comparative proteome profiling study, analyzing primary human fibroblast-like cells isolated from the bone marrow of MM, of MGUS, as well as of non-neoplastic control patients. Thereby, a group of extracellular matrix (ECM) proteins, ECM receptors, and ECM-modulating enzymes turned out to be progressively up-regulated in MGUS and MM. These proteins include laminin α4, lysyl-hydroxylase 2, prolyl 4-hydroxylase 1, nidogen-2, integrin α5β5, c-type mannose receptor 2, PAI-1, basigin, and MMP-2, in addition to PDGF-receptor β and the growth factor periostin, which are likewise involved in ECM activities. Our results indicate that ECM remodeling by fibroblast-like cells may take place already at the level of MGUS and may become even more pronounced in MM. The identified proteins which indicate the stepwise progression from MGUS to MM may offer new tools for therapeutic strategies.
authors.affiliation: Faculty of Chemistry, Institute of Analytical Chemistry, University of Vienna , Währingerstraße 38, A-1090 Vienna, Austria.
authors.forename: Astrid
authors.initials: A
authors.lastname: Slany
authors.forename: Verena
authors.initials: V
authors.lastname: Haudek-Prinz
authors.forename: Anastasia
authors.initials: A
authors.lastname: Meshcheryakova
authors.forename: Andrea
authors.initials: A
authors.lastname: Bileck
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lamm
authors.forename: Christoph
authors.initials: C
authors.lastname: Zielinski
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerner
authors.forename: Johannes
authors.initials: J
authors.lastname: Drach
mesh_terms: D001854:Bone Marrow Cells / Q000378:metabolism*; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*