Abnormalities of bone marrow mesenchymal cells in multiple myeloma patients

BACKGROUND. The importance of the bone marrow microenvironment in multiple myeloma is receiving increasing attention. Recent studies have suggested th e importance of cytokine production and cell-cell contact by bone marrow st romal cells in the survival of myeloma cells. METHODS. In the current study, the authors examined bone marrow mesenchymal progenitor cell (MPC) cultures derived from eight multiple myeloma patient s (mean age, 58 years) and nine normal donors (mean age, 61 years), with em phasis on cell surface antigens, cytokine, and growth factor expression. RESULTS. The authors have found, based on analysis of cellular receptors, g rowth factors, and cytokine expression, that myeloma MPCs are phenotypicall y and functionally distinguishable from normal donor MPCs. Immunofluorescen ce analysis of MPC monolayers shows that myeloma MPC cultures expressed red uced cell surface vascular cell adhesion molecule-1 and fibronectin, in con trast with the strong expression found on normal donor MPCs. Furthermore, a subset of myeloma MPCs strongly express intracellular receptor for hyaluro nan-mediated motility, whereas normal MPCs do not. Cytokine expression in b one marrow MPC cultures was examined by reverse transcription-polymerase ch ain reaction and enzyme linked immunosorbent assay. Bone marrow MPCs consti tutively express interleukin (IL)-1 beta, IL-6, granulocyte colony-stimulat ing factor (G-CSF), granule cyte macrophage (GM)-CSF, stem cell factor (SCF ), and tumor necrosis factor (TNF)-alpha.. In comparison to normal MPCs, mu ltiple myeloma MPCs express increased basal levels of IL-1 beta and TNF-alp ha. In vitro exposure of MPC cultures to dexamethasone resulted in the down -regulation of IL-6, G-CSF, and GM-CSF in both normal and myeloma MPC cultu res. However, dexamethasone treatment significantly increased expression of SCF-1 in myeloma MPCs. CONCLUSIONS. in myeloma, bone marrow stromal cells provide paracrine factor s, through cytokine production and cell-cell contact, which play a role in plasma cell growth and survival. The authors' data indicate differences in bone marrow MPCs, which may be biologically relevant to the growth and surv ival of myeloma plasma cells. (C) 2001 American Cancer Society.