title: Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis.
abstract: Patients with multiple myeloma (MM) have increased bone marrow (BM) angiogenesis; however, the proangiogenic properties of myeloma cells and the mechanisms of MM-induced angiogenesis are not completely clarified. The angiopoietin system has been identified as critical in the regulation of vessel formation. In this study we have demonstrated that myeloma cells express several proangiogenic factors, and, in particular, we found that angiopoietin-1 (Ang-1), but not its antagonist Ang-2, was expressed by several human myeloma cell lines (HMCLs) at the mRNA and the protein levels. In a transwell coculture system, we observed that myeloma cells up-regulated the Ang-1 receptor Tie2 in human BM endothelial cells. Moreover, in an experimental model of angiogenesis, the conditioned medium of HMCLs significantly stimulated vessel formation compared with control or vascular endothelial growth factor (VEGF) treatment. The presence of anti-Tie2 blocking antibody completely blunted the proangiogenic effect of XG-6. Finally, our in vitro results were supported by the in vivo finding of Ang-1, but not Ang-2, mRNA and protein expression in purified MM cells obtained from approximately 47% of patients and by high BM angiogenesis in patients with MM positive for Ang-1, suggesting that the angiopoietin system could be involved, at least in part, in MM-induced angiogenesis.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, Institute of Medical Pathology, University of Parma, Italy. n_giuliani@yahoo.com
authors.forename: Nicola
authors.initials: N
authors.lastname: Giuliani
authors.forename: Simona
authors.initials: S
authors.lastname: Colla
authors.forename: Mirca
authors.initials: M
authors.lastname: Lazzaretti
authors.forename: Roberto
authors.initials: R
authors.lastname: Sala
authors.forename: Giovanni
authors.initials: G
authors.lastname: Roti
authors.forename: Cristina
authors.initials: C
authors.lastname: Mancini
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bonomini
authors.forename: Paolo
authors.initials: P
authors.lastname: Lunghi
authors.forename: Magda
authors.initials: M
authors.lastname: Hojden
authors.forename: Giovenzio
authors.initials: G
authors.lastname: Genestreti
authors.forename: Mirija
authors.initials: M
authors.lastname: Svaldi
authors.forename: Paolo
authors.initials: P
authors.lastname: Coser
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Fattori
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sammarelli
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Gazzola
authors.forename: Regis
authors.initials: R
authors.lastname: Bataille
authors.forename: Camillo
authors.initials: C
authors.lastname: Almici
authors.forename: Cecilia
authors.initials: C
authors.lastname: Caramatti
authors.forename: Lina
authors.initials: L
authors.lastname: Mangoni
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rizzoli
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007952:Leukemia, Plasma Cell / Q000378:metabolism / Q000473:pathology; D008222:Lymphokines / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D042787:Receptor, TIE-2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: C467630:ANGPT1 protein, human; D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C105373:MEN1 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D042787:Receptor, TIE-2