The myeloma cell antigen syndecan-1 is lost by apoptotic myeloma cells.
Syndecan-1 is a cell membrane proteoglycan that binds extracellular matrix components and various growth factors. It is expressed only on malignant plasma cells in bone marrow samples from patients with multiple myeloma (MM). Several reports have suggested that syndecan-1 was present only on a part of the myeloma cells. By using either IL-6-dependent myeloma cell lines or primary myeloma cells stained by annexin V, we report here that syndecan-1 was rapidly lost by myeloma cells undergoing apoptosis. In the same experimental conditions, expression of other cell membrane antigens such as CD38, HLA class-I or CD49d on apoptotic myeloma cells was not affected. In addition, we show that syndecan-1 loss was independent of activation of the gp130 IL-6 transducer. Dexamethasone induced a strong apoptosis of myeloma cells associated with the loss of syndecan-1. Finally, by using freshly-explanted tumoural samples, we show that syndecan-1 rapidly disappeared from myeloma cells in association with induction of apoptosis. In conclusion we showed that syndecan-1 is a marker for viable myeloma cells which is rapidly lost by apoptotic cells. These results emphasize the usefulness of anti-syndecan-1 antibodies to purge tumoural cells from haemopoietic grafts or to purify these cells for further manipulations for immuno or gene therapies.
Jourdan
M
M
INSERM U475, Montpellier, France.
Ferlin
M
M
Legouffe
E
E
Horvathova
M
M
Liautard
J
J
Rossi
J F
JF
Wijdenes
J
J
Brochier
J
J
Klein
B
B
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D017304:Annexin A5 / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000032:analysis; D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D050822:Cytokine Receptor gp130; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D009244:NAD+ Nucleosidase / Q000032:analysis; D011509:Proteoglycans / Q000378:metabolism*; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D015703:Antigens, CD; D000943:Antigens, Differentiation; C494199:IL6ST protein, human; D016898:Interferon-alpha; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D050822:Cytokine Receptor gp130; D003907:Dexamethasone; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1