title: Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells.
abstract: Notch receptors expressed on hematopoietic stem cells interact with their ligands on bone marrow stromal cells and thereby control cell fate decisions and survival. We recently demonstrated that Notch signaling is involved in proliferation and survival of B cell-derived tumor cells of classic Hodgkin disease and described a novel mechanism for the oncogenic capacity of Notch. In this study we investigated whether Notch signaling is involved in the tight interactions between neoplastic plasma cells and their bone marrow microenvironment, which are essential for tumor cell growth in multiple myeloma (MM). Here we demonstrate that Notch receptors and their ligand Jagged1 are highly expressed in cultured and primary MM cells, whereas nonneoplastic counterparts show low to undetectable levels of Notch. Functional data indicate that ligand-induced Notch signaling is a growth factor for MM cells and suggest that these interactions contribute to myelomagenesis in vivo.
authors.affiliation: Department of Hematology and Oncology, Charité, Campus Virchow-Klinikum, University Medicine Berlin, Berlin, Germany. fjundt@mdc-berlin.de
authors.forename: Franziska
authors.initials: F
authors.lastname: Jundt
authors.forename: Kristina Schulze
authors.initials: KS
authors.lastname: Pröbsting
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.forename: Gwendolin
authors.initials: G
authors.lastname: Muehlinghaus
authors.forename: Manik
authors.initials: M
authors.lastname: Chatterjee
authors.forename: Stephan
authors.initials: S
authors.lastname: Mathas
authors.forename: Ralf C
authors.initials: RC
authors.lastname: Bargou
authors.forename: Rudolf
authors.initials: R
authors.lastname: Manz
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
mesh_terms: D001402:B-Lymphocytes / Q000737:chemistry; D001854:Bone Marrow Cells / Q000737:chemistry; D002135:Calcium-Binding Proteins; D002450:Cell Communication; D002455:Cell Division; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D009101:Multiple Myeloma / Q000209:etiology / Q000473:pathology*; D011506:Proteins / Q000032:analysis / Q000502:physiology; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology*; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014157:Transcription Factors
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; D011506:Proteins; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors