title: Fibroblast growth factor receptor 3 (FGFR3) associated with the CD20 antigen regulates the rituximab-induced proliferation inhibition in B-cell lymphoma cells.
abstract: Rituximab is reported to inhibit the proliferation of lymphoma cells through an unknown CD20-mediated signal transduction pathway. Herein, we investigated cell surface molecules involved in the CD20-mediated signal transduction pathway by using a recently developed technique named enzyme-mediated activation of radical sources. Using this method, we found that under stimulation with rituximab and another anti-CD20 antibody B-Ly1, CD20 was physically associated with fibroblast growth factor receptor 3 (FGFR3) as well as some other receptor tyrosine kinases in Raji cells. However, under stimulation with a noncytotoxic anti-CD20 antibody 2H7, CD20 was not associated with FGFR3 but with the PDGF receptor β. When the tyrosine kinase activity of FGFR3 was inhibited by the chemical inhibitor PD173074 or an siRNA knockdown strategy, the proliferation inhibition by rituximab was attenuated, indicating that FGFR3 participates in the rituximab-dependent signal transduction pathway leading to proliferation inhibition. These observations raise the possibility that concomitant targeted therapy toward FGFR3 might improve the efficacy and safety of the rituximab therapy.
authors.affiliation: Department of Biochemistry, Saitama Medical University, Iruma-gun, Saitama, 350-0495, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kotani
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ishiura
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Yamashita
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Honke
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D018951:Antigens, CD20; D000970:Antineoplastic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D016393:Lymphoma, B-Cell; D021962:Membrane Microdomains / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000069283:Rituximab; D015398:Signal Transduction
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; C115711:PD 173074; D011743:Pyrimidines; D000069283:Rituximab; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; C505407:CASP3 protein, human; D053148:Caspase 3