title: Bortezomib influences the expression of malignant plasma cells membrane antigens.
abstract: Multiple myeloma cells can be characterized immunophenotypically as the expression levels of several membrane antigens differ from those of normal plasma cells. These antigens are important for making a diagnostic of multiple myeloma; they have a significant role in survival and proliferation of multiple myeloma cells. Analyzing the effect of bortezomib on the expression of surface antigens CD138, CD56, CD27, CD28, CD45 and CD221 and xenograft models, we have found that bortezomib increases the level of CD45 and decreases all other antigens. Bortezomib induces the reduction of IGF-1R (CD221) and syndecan 1 (CD138). This effect was associated with the reduced activation of Ras/MAPK, mTOR/p70S6K and JAK/STAT pathways in response to IGF-1 and IL-6. These results suggest that bortezomib may influence the sensitivity of myeloma cells to soluble growth factors by down-regulation of membrane receptors.
authors: Université de Lyon, F-69008, Lyon, France.
authors: Ines
authors: I
authors: Tagoug
authors: Adriana
authors: A
authors: Plesa
authors: Charles
authors: C
authors: Dumontet
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000378:metabolism*; D010950:Plasma Cells / Q000187:drug effects / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000941:Antigens; D000970:Antineoplastic Agents; D001897:Boronic Acids; D015850:Interleukin-6; D008565:Membrane Proteins; D061988:Proteasome Inhibitors; D011719:Pyrazines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007334:Insulin-Like Growth Factor I; D000069286:Bortezomib; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases