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The myeloma cell antigen syndecan-1 is lost by apoptotic myeloma cells
M Jourdan1, M Ferlin, E Legouffe
1INSERM U475, Montpellier, France.
Abstract:
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.
Insights
Syndecan-1 is lost from multiple myeloma cells during apoptosis, unlike other cell markers. This finding highlights syndecan-1 as a marker for viable myeloma cells, useful for cell purging and purification therapies.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Syndecan-1 is a cell membrane proteoglycan found on malignant plasma cells in multiple myeloma (MM).
- Previous studies suggested syndecan-1 expression varied among myeloma cells.
- The precise behavior of syndecan-1 during myeloma cell death was not fully understood.
Purpose of the Study:
- To investigate the expression dynamics of syndecan-1 in multiple myeloma cells undergoing apoptosis.
- To determine if syndecan-1 loss during apoptosis is specific or affects other cell surface markers.
- To explore the potential therapeutic applications of syndecan-1 as a marker for viable myeloma cells.
Main Methods:
- Utilized IL-6-dependent myeloma cell lines and primary myeloma cells.
- Employed annexin V staining to identify apoptotic cells.
- Monitored syndecan-1 expression alongside other cell membrane antigens (CD38, HLA class-I, CD49d) during apoptosis.
- Investigated the role of gp130 IL-6 transducer activation and dexamethasone treatment.
Main Results:
- Syndecan-1 was rapidly lost from myeloma cells undergoing apoptosis.
- Expression of CD38, HLA class-I, and CD49d remained unaffected on apoptotic myeloma cells.
- Syndecan-1 loss was independent of gp130 IL-6 transducer activation.
- Dexamethasone treatment induced myeloma cell apoptosis and syndecan-1 loss.
- Freshly explanted tumor samples confirmed rapid syndecan-1 disappearance with induced apoptosis.
Conclusions:
- Syndecan-1 serves as a marker for viable multiple myeloma cells.
- Apoptotic myeloma cells rapidly lose syndecan-1 expression.
- Anti-syndecan-1 antibodies can be utilized for purging tumor cells from hematopoietic grafts.
- Syndecan-1 expression data aids in purifying myeloma cells for immunotherapy and gene therapy.