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Biomedical subjects

M Ferlin

Publications and source records attributed to M Ferlin.

3 recordsLinked to original sources

Malignant plasma cell lines express a functional CD28 molecule.

The function of CD28 molecules that are present on malignant plasma cells of human myeloma cell lines (HMCL) was studied. First, myeloma cells expressed a similar density of CD28 antigen to that of normal T cells. The myeloma CD28 molecules were able to bind B7-Ig molecules as well as L cells transfected with a B7-1 cDNA, and anti-CD28 mAb inhibited the binding. Myeloma cells did not express B7-1 antigens but a low density of B7-2 antigens. The myeloma B7-2 molecules of two HMCL were able to bind CTLA-4 protein. No autocrine CD28:B7-2 activation could be evidenced as we found no spontaneous binding of the p85 subunit of PI-3 kinase to CD28 molecules. In addition, a blocking anti-CD28 mAb did not affect the IL-6-dependent or autonomous proliferation of the HMCL. The activation of myeloma CD28 molecules with or without TPA stimulation did not affect the proliferation, survival, differentiation, expression of activation antigens and cytokine receptors or cytokine production of myeloma cells. However, the triggering of myeloma CD28 molecules by B7-1 transfectant cells resulted in binding of the p85 subunit of PI-3 kinase to CD28 molecules as previously shown for T cell CD28 molecules. This expression of a large density of CD28 molecules able to bind B7 molecules might contribute to a downregulation of the immune control of myeloma cells.

B7-1 Antigen

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.

ADP-ribosyl Cyclase

Anti-apoptotic activity of low levels of wild-type p53.

Induction of apoptosis is a function of both an external stimulus and the physiology of the cell, which includes the expression of multiple oncogenes and tumor suppressors. Here we have studied the apoptotic response of immortalized mouse fibroblasts to serum withdrawal. We show that, in addition to the p53-independent apoptosis observed in p53- cells, overexpression of wild-type p53 tumor suppressor results in a high rate of programmed cell death. However, physiological range, low levels of the p53 protein protect fibroblasts from induction of apoptosis. Our results indicate that, as a function of its dose, the wild-type p53 can either protect from death or promote apoptosis. This new, anti-apoptotic, activity of p53 may have implications for the understanding of the role played by p53 in embryonic development as well as in initial stages of oncogenesis.

3T3 Cells