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 the importance of cytokine production and cell-cell contact by bone marrow stromal 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 patients (mean age, 58 years) and nine normal donors (mean age, 61 years), with emphasis on cell surface antigens, cytokine, and growth factor expression.


RESULTS
The authors have found, based on analysis of cellular receptors, growth factors, and cytokine expression, that myeloma MPCs are phenotypically and functionally distinguishable from normal donor MPCs. Immunofluorescence analysis of MPC monolayers shows that myeloma MPC cultures expressed reduced cell surface vascular cell adhesion molecule-1 and fibronectin, in contrast with the strong expression found on normal donor MPCs. Furthermore, a subset of myeloma MPCs strongly express intracellular receptor for hyaluronan-mediated motility, whereas normal MPCs do not. Cytokine expression in bone marrow MPC cultures was examined by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay. Bone marrow MPCs constitutively express interleukin (IL)-1beta, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage (GM)-CSF, stem cell factor (SCF), and tumor necrosis factor (TNF)-alpha. In comparison to normal MPCs, multiple myeloma MPCs express increased basal levels of IL-1beta and TNF-alpha. 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 cultures. However, dexamethasone treatment significantly increased expression of SCF-1 in myeloma MPCs.


CONCLUSIONS
In myeloma, bone marrow stromal cells provide paracrine factors, 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 survival of myeloma plasma cells.
Virginia Piper Cancer Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
S R
SR
Wallace
M M
MM
Oken
K L
KL
Lunetta
A
A
Panoskaltsis-Mortari
A M
AM
Masellis
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000032:analysis; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D018931:Antineoplastic Agents, Hormonal; D016207:Cytokines; D006133:Growth Substances; D016023:Integrins; D003907:Dexamethasone