Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis

Autor: Mirca Lazzaretti, Roberto Sala, Gian C. Gazzola, Mirija Svaldi, Pier Paolo Fattori, Lina Mangoni, Magda Hojden, Paolo Lunghi, Giovanni Roti, Nicola Giuliani, Camillo Almici, Gabriella Sammarelli, Simona Colla, P. Coser, Sabrina Bonomini, Vittorio Rizzoli, Cristina Mancini, Régis Bataille, Giovenzio Genestreti, Cecilia Caramatti
Rok vydání: 2003
Předmět:
Vascular Endothelial Growth Factor A
Angiogenesis
Endothelial Growth Factors
Biochemistry
Leukemia
Plasma Cell
Neovascularization
chemistry.chemical_compound
RNA
Neoplasm
Lymphokines
Membrane Glycoproteins
Neovascularization
Pathologic
biology
Vascular Endothelial Growth Factors
Antibodies
Monoclonal
Hematology
Middle Aged
Receptor
TIE-2
Angiopoietin receptor
Neoplasm Proteins
Gene Expression Regulation
Neoplastic
Vascular endothelial growth factor
Vascular endothelial growth factor A
medicine.anatomical_structure
Angiopoietin-1
cardiovascular system
Intercellular Signaling Peptides and Proteins
medicine.symptom
Multiple Myeloma
Adult
medicine.medical_specialty
Immunology
Bone Marrow Cells
Angiopoietin-2
Angiopoietin
Proto-Oncogene Proteins
Internal medicine
medicine
Humans
Endothelium
RNA
Messenger
business.industry
Cell Biology
Coculture Techniques
Endocrinology
chemistry
Culture Media
Conditioned
Cancer research
biology.protein
Angiogenesis Inducing Agents
Bone marrow
business
Zdroj: Blood. 102:638-645
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood-2002-10-3257
Popis: 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.
Databáze: OpenAIRE
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