Requirement of soluble factors produced by bone marrow stromal cells on the growth of novel established human myeloma cell line.
The growth of myeloma cells is believed to be mediated by functional interactions between tumor cells and the marrow environment involving the action of several cytokines. We report on the establishment and characterization of a new human myeloma cell line (TAB1) that can be long-term maintained in the presence of conditioned medium of bone marrow stromal cells (BMCM) and a BMCM independent variant, C2-2. Both cell lines have plasma cell morphology and express plasma cell antigens (CD38, PCA-1 and immunoglobulin kappa light chain). In the absence of BMCM, TAB1 cells undergoing apoptosis were observed. Among the adherent molecules tested, these cells expressed VLA-4, ICAM-1 and H-CAM, but not VLA-5, suggesting that these were mostly immature plasmacytes. Introduction with exogenous IL-6 and/or GM-CSF, which were detected in BMCM, partially supported the proliferation of TAB1 cells. Treatment with anti-IL-6 antibody partially inhibited the proliferation of TAB1 cells cultured with BMCM. These findings strongly suggest that TAB1 required at least two or more factors on their growth in vitro; IL-6 was one of the factors necessary for cell growth. Further studies are required to clarify the precise molecules which support TAB1 cell growth in combination with IL-6, however, TAB1 and its variant C2-2 cells may offer an attractive model to unravel novel molecular mechanisms involved in bone marrow stroma-dependent growth of myeloma cells.
Aikawa
Shingo
S
Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Hatta
Yoshihiro
Y
Tanaka
Megumi
M
Kaneita
Yoshitaka
Y
Yasukawa
Kiyotaka
K
Sawada
Umihiko
U
Horie
Takashi
T
Tsuboi
Isao
I
Aizawa
Shin
S
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001685:Biological Factors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D018920:Coculture Techniques; D005091:Exons / Q000235:genetics; D017809:Fatal Outcome; D016259:Genes, myc; D016158:Genes, p53; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006133:Growth Substances / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology; D008297:Male; D009101:Multiple Myeloma / Q000473:pathology*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D001685:Biological Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances; D015850:Interleukin-6; D011994:Recombinant Proteins; D000093242:Interleukin-6 Inhibitors