Anti-CD20 therapeutic antibody rituximab modifies the functional organization of rafts/microdomains of B lymphoma cells

Article Article scientifique Article Anti-CD20 therapeutic antibody rituximab modifies the functional organization of rafts/microdomains of B lymphoma cells eng 2003 author Semac Isabelle 521725 author Palomba Carmen 132782 author Kulangara Karina author Klages Natacha author van Echten-Deckert Gerhild author Borisch Bettina 104254 author Hoessli Daniel 25326 534-540 12543813 0008-5472 http://cancerres.aacrjournals.org/content/63/2/534.full.pdf Incubation of Burkitt lymphoma-derived Raji cells at physiological temperature with submicromolar concentrations of humanized anti-CD20 antibody rituximab (RTX) redistributes CD20 to liquid-ordered, plasma membrane rafts. This accumulation of the CD20 tetraspan protein in rafts does not change the existing lipid and phosphoprotein composition but makes sphingolipids and the Src regulator Cbp/PAG (Csk-binding protein/phosphoprotein associated with glycosphingolipid-enriched microdomain) transmembrane phosphoprotein more resistant to n-octyl-beta-pyranoside, a detergent that dissociates sphingolipid clusters. On the contrary, sphingolipids and Cbp/PAG are not protected by the presence of CD20 against the disruptive effects of methyl-beta-cyclodextrin, a cyclic carbohydrate that removes membrane cholesterol. After accumulation of CD20, the activity of the raft-associated Lyn kinase is down-regulated without apparent alteration of its relationship to substrates. Moreover, in rafts of lymphoblastoid cells that express lower amounts of Cbp/PAG, RTX redistributes CD20 to rafts but does not modulate the raft-associated protein tyrosine kinase activity, suggesting that the presence of Cbp/PAG protein in rafts is necessary for RTX to exert its transmembrane "signaling effects." Lastly, redistribution of CD20 in rafts renders the glycosylphosphatidyl inositol (GPI)-linked CD55 C'-defense protein hypersensitive to glycosylphosphatidyl inositol-specific phospholipases. By redistributing CD20 to rafts, RTX modifies their stability and organization and modulates the associated signaling pathways and C' defense capacity. Antibodies, Monoclonal/ pharmacology Antigens, CD20/ metabolism Antigens, CD55/metabolism Antineoplastic Agents/ pharmacology Cyclodextrins/chemistry Glucosides/chemistry Humans Lymphoma, B-Cell/drug therapy/ metabolism Membrane Lipids/metabolism Membrane Microdomains/drug effects/ metabolism Membrane Proteins/metabolism Phospholipase D/metabolism Phosphoproteins/metabolism Type C Phospholipases/metabolism beta-Cyclodextrins src-Family Kinases/metabolism Dewey 616.07 true Cancer research 63 2 2e8a50a8-fa9c-45b4-bc43-74f25337b1d7 Article Restricted file1.pdf 196071 application/pdf restrictedAccess

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Anti-CD20 therapeutic antibody rituximab modifies the functional organization of rafts/microdomains of B lymphoma cells	Cancer research			2003	668	0

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