Rituximab inhibits B-cell receptor signaling
| Autor: | Guy Laurent, S Kheirallah, Jean-Jacques Fournié, Anne Quillet-Mary, Christine Bezombes, Pierre Caron, Emilie Gross, Justine Bertrand-Michel |
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| Přispěvatelé: | Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'hématologie [Hôpital Purpan, Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Claudius Regaud-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Plateforme MetaToul, MetaboHUB |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
MAPK/ERK pathway
Time Factors [SDV]Life Sciences [q-bio] Cell Syk Biochemistry Antibodies Monoclonal Murine-Derived 0302 clinical medicine hemic and lymphatic diseases Receptor Extracellular Signal-Regulated MAP Kinases Cells Cultured ComputingMilieux_MISCELLANEOUS 0303 health sciences Protein Tyrosine Phosphatase Non-Receptor Type 6 breakpoint cluster region Intracellular Signaling Peptides and Proteins Antibodies Monoclonal Hematology Protein-Tyrosine Kinases Flow Cytometry 3. Good health medicine.anatomical_structure Cholesterol src-Family Kinases 030220 oncology & carcinogenesis [SDV.IMM]Life Sciences [q-bio]/Immunology RNA Interference Signal transduction Rituximab Signal Transduction Immunology Blotting Western Receptors Antigen B-Cell [SDV.CAN]Life Sciences [q-bio]/Cancer Biology 03 medical and health sciences Membrane Microdomains LYN Cell Line Tumor medicine Humans Syk Kinase Protein kinase B 030304 developmental biology Phospholipase C gamma Cell Biology Cancer research Calcium Proto-Oncogene Proteins c-akt |
| Zdroj: | Blood Blood, American Society of Hematology, 2010, 115 (5), pp.985-994. ⟨10.1182/blood-2009-08-237537⟩ |
| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood-2009-08-237537⟩ |
| Popis: | Rituximab (RTX), a monoclonal antibody directed against the CD20 protein, is a drug commonly used in the treatment of B-cell–derived lymphoid neoplasias and of antibody-mediated autoimmune diseases. In addition to cell- and complement-mediated B-cell depletion, RTX is thought to inhibit B-cell survival and proliferation through negative regulation of canonical signaling pathways involving Akt, ERK, and mammalian target of rapamycin. However, surprisingly, although B-cell receptor (BCR) signaling has been considered critical for normal and more recently, for neoplastic B cells, the hypothesis that RTX could target BCR has never been investigated. Using follicular lymphoma cell lines as models, as well as normal B cells, we show here, for the first time, that pretreatment with RTX results in a time-dependent inhibition of the BCR-signaling cascade involving Lyn, Syk, PLCγ2, Akt, and ERK, and calcium mobilization. The inhibitory effect of RTX correlates with decrease of raft-associated cholesterol, complete inhibition of BCR relocalization into lipid raft microdomains, and down-regulation of BCR immunoglobulin expression. Thus, RTX-mediated alteration of BCR expression, dynamics, and signaling might contribute to the immunosuppressive activity of the drug. |
| Databáze: | OpenAIRE |
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