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

Nicola Giuliani, Simona Colla, Mirca Lazzaretti, Roberto Sala, Giovanni Roti, Cristina Mancini, Sabrina Bonomini, Paolo Lunghi, Magda Hojden, Giovenzio Genestreti, Mirija Svaldi, Paolo Coser, Pier Paolo Fattori, Gabriella Sammarelli, Gian Carlo Gazzola, Regis Bataille, Camillo Almici, Cecilia Caramatti, Lina Mangoni, Vittorio Rizzoli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)638-645
Number of pages8
JournalBlood
Volume102
Issue number2
DOIs
Publication statusPublished - Jul 15 2003

ASJC Scopus subject areas

  • Hematology

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    Giuliani, N., Colla, S., Lazzaretti, M., Sala, R., Roti, G., Mancini, C., Bonomini, S., Lunghi, P., Hojden, M., Genestreti, G., Svaldi, M., Coser, P., Fattori, P. P., Sammarelli, G., Gazzola, G. C., Bataille, R., Almici, C., Caramatti, C., Mangoni, L., & Rizzoli, V. (2003). Proagiogenic properties of human myeloma cells: Production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis. Blood, 102(2), 638-645. https://doi.org/10.1182/blood-2002-10-3257