title: Stable changes in mesenchymal stromal cells from multiple myeloma patients revealed through their responses to Toll-like receptor ligands and epidermal growth factor.
abstract: In human multiple myeloma (MM), the tumor cells exhibit strict dependence on bone marrow (BM) stromal elements. It has been suggested that, in turn, MM cells modify multipotent stromal cells (MSCs), diverting them to support the myeloma. We investigated MM-derived MSCs by comparing their toll-like receptor (TLR) responses to those of MSCs derived from healthy controls. We now report that MM-derived MSCs manifested intact proliferation responses and IL-6 secretion and their adipose and osteogenic differentiation responses to TLR ligands were also similar to those of healthy controls, ranging from augmentation to inhibition. However, MM-derived MSCs were found to be defective in IL-8 secretion and ERK1/2 phosphorylation following TLR-2 activation. Moreover, MM-derived MSCs failed to respond to EGF by elevation of ERK1/2 phosphorylation. The persistence of these changes in extensively cultured MM-derived MSCs, suggests that these cells are stably, if not irreversibly modified.
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Meirav
authors: M
authors: Pevsner-Fischer
authors: Sarit
authors: S
authors: Levin
authors: Tal
authors: T
authors: Hammer-Topaz
authors: Yifat
authors: Y
authors: Cohen
authors: Felix
authors: F
authors: Mor
authors: Gerard
authors: G
authors: Wagemaker
authors: Arnon
authors: A
authors: Nagler
authors: Irun Robert
authors: IR
authors: Cohen
authors: Dov
authors: D
authors: Zipori
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008074:Lipoproteins / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; D008024:Ligands; D008074:Lipoproteins; D051193:Toll-Like Receptors; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases