Mesenchymal stem cell abnormalities in patients with multiple myeloma
Résumé
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.
Mots clés
cell protein
Dickkopf factor
growth factor receptor
unclassified drug
adult
aged
article
bone development
bone lesion
bone marrow cell
cell function
cell growth
cell surface
clinical article
controlled study
down regulation
female
human
human cell
in vitro study
male
mesenchymal stem cell
multiple myeloma
nucleotide sequence
osteolysis
priority journal
protein expression
reverse transcription polymerase chain reaction
Aged
Bone and Bones
Cell Differentiation
Female
Gene Expression Regulation
Neoplastic
Humans
Immunophenotyping
Intercellular Signaling Peptides and Proteins
Interleukin-6
Male
Mesenchymal Stem Cells
Middle Aged
Multiple Myeloma
Osteoblasts
Osteoclasts
Osteolysis
Syndecan-1