A possible role for the loss of CD27-CD70 interaction in myelomagenesis.
CD27 is a marker of memory B cells and its interaction with its ligand, CD70, is very important for differentiation into plasma cells. Although CD27 is detected on normal plasma cells, its expression is significantly reduced with the progression of multiple myeloma (MM), including monoclonal gammopathy of undetermined significance (MGUS). CD27+ myeloma cells are thought to represent an early phase of myeloma, as CD27+ plasma cells from MM patients were found to be composed of normal plasma cells (CD19+/CD38++) and myeloma cells (CD19-/CD38++), and monoclonality was detected in the CD27+/CD38++ fraction. Given that the lack of CD27 on plasma cells is related to myelomagenesis and that the pro-apoptotic protein Siva is thought to bind to the cytoplasmic tail of CD27, we analysed alterations of cell growth and genes caused by co-culturing CD27-transfected myeloma cell lines (U266, KMS-5) with CD70-transfected NIH3T3 cells. CD27-CD70 interaction could not induce apoptosis in either type of myeloma transfectant, and binding between Siva and CD27 was not detected. cDNA microarray (human apoptosis CHIP) analysis showed a significant upregulation of expression of the ectodermal neural cortex 1 (ENC1) gene by CD27-CD70 interaction compared with CD27 transfection alone. These findings show that the relationship between the loss of CD27 and oncogenesis of plasma cells is not simple. It remains unclear whether the lack of CD27 leads to evasion of apoptosis.
Katayama
Yuta
Y
Department of Haematology and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan.
Sakai
Akira
A
Oue
Naohide
N
Asaoku
Hideki
H
Otsuki
Takemi
T
Shiomomura
Takeshi
T
Masuda
Rie
R
Hino
Norihiko
N
Takimoto
Yasuo
Y
Imanaka
Fumio
F
Yasui
Wataru
W
Kimura
Akiro
A
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D053282:CD27 Ligand; D002352:Carrier Proteins / Q000378:metabolism; D016022:Case-Control Studies; D018920:Coculture Techniques; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009101:Multiple Myeloma / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D053282:CD27 Ligand; C505771:CD70 protein, human; D002352:Carrier Proteins; C505772:Cd70 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C106549:SIVA1 protein, human; C484569:Siva protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7