title: Mesenchymal stem cell abnormalities in patients with multiple myeloma.
abstract: Osteolytic bone lesions are common in patients with multiple myeloma (MM), a clonal plasma cell disorder, and result from increased osteoclastic bone resorption and decreased osteoblastic bone formation. Because mesenchymal stem cells (MSCs) are committed towards cells of the osteoblast lineage, we compared the in vitro characteristics of MSCs from the bone marrow of 18 MM patients (MM-MSCs) and eight normal donors (ND-MSCs). MM-MSCs displayed deficient growth that could be explained in part by the reduced expression of several growth factor receptors on the surface of MM-MSCs compared with ND-MSCs. Receptor downregulation was observed on RT-PCR analysis. A major finding was an approximately fivefold higher expression of osteoblast inhibitor DKK1 at transcript and protein levels in MM-MSCs than ND-MSCs. These data suggest that defective osteoblast function in patients with advanced MM may be related not only to factors released by tumor myeloma cells but also to MSC abnormalities.
authors.affiliation: INSERM, U832, EA1638, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.forename: Christelle
authors.initials: C
authors.lastname: Mazurier
authors.forename: Alain
authors.initials: A
authors.lastname: Chapel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ernou
authors.forename: Laetitia
authors.initials: L
authors.lastname: Boutin
authors.forename: Xavier
authors.initials: X
authors.lastname: Holy
authors.forename: Norbert Claude
authors.initials: NC
authors.lastname: Gorin
authors.forename: Manuel
authors.initials: M
authors.lastname: Lopez
authors.forename: Christelle
authors.initials: C
authors.lastname: Doucet
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lataillade
mesh_terms: D000368:Aged; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000473:pathology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010014:Osteolysis; D053668:Syndecan-1 / Q000096:biosynthesis
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D053668:Syndecan-1