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Extracellular Matrix Remodeling by Bone Marrow Fibroblast-like Cells Correlates with Disease Progression in Multiple Myeloma
journal contribution
posted on 2014-02-07, 00:00 authored by Astrid Slany, Verena Haudek-Prinz, Anastasia Meshcheryakova, Andrea Bileck, Wolfgang Lamm, Christoph Zielinski, Christopher Gerner, Johannes DrachThe
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.