title: Critical role of the NOTCH ligand JAG2 in self-renewal of myeloma cells.
abstract: The purpose of this study was to identify the pathways associated with the ability of CD138(+) human myeloma cells to form colonies in a serum-free semi-solid human collagen-based assay. Only 26% (7 of 27) of human myeloma cell lines were able to spontaneously form colonies. This spontaneous clonogenic growth correlated with the expression of the NOTCH ligand JAG2 (p<0.001). Blocking JAG-NOTCH interactions with NOTCH-Fc chimeric molecules impaired self-colony formation, indicating a role for JAG-NOTCH pathway in colony formation. In two cell lines, silencing of JAG2 blocked both colony formation and in vivo tumor formation in immunocompromised mice. RT-PCR and flow cytometry analysis revealed that JAG2 is often expressed by CD138(+) primary cells. Our results indicate that spontaneous clonogenic growth of myeloma cells requires the expression of JAG2.
authors.affiliation: INSERM, UMR_S892, Nantes, F-44007, France.
authors.forename: David
authors.initials: D
authors.lastname: Chiron
authors.forename: Sophie
authors.initials: S
authors.lastname: Maïga
authors.forename: Géraldine
authors.initials: G
authors.lastname: Descamps
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.forename: Séverine
authors.initials: S
authors.lastname: Marionneau
authors.forename: Thibauld
authors.initials: T
authors.lastname: Ouiller
authors.forename: Jérôme
authors.initials: J
authors.lastname: Moreaux
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
authors.forename: Régis
authors.initials: R
authors.lastname: Bataille
authors.forename: Martine
authors.initials: M
authors.lastname: Amiot
authors.forename: Catherine
authors.initials: C
authors.lastname: Pellat-Deceunynck
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072101:Jagged-2 Protein; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D053668:Syndecan-1 / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C490504:JAG2 protein, human; D000072101:Jagged-2 Protein; D008024:Ligands; D008565:Membrane Proteins; D051880:Receptors, Notch; D053668:Syndecan-1