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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-10-3257. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3257v1 102/2/638    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Giuliani, N. Articles by Rizzoli, V. Search for Related Content PubMed PubMed Citation Articles by Giuliani, N. Articles by Rizzoli, V. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 638-645 NEOPLASIA Proangiogenic 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, and Vittorio Rizzoli From the Hematology and Bone Marrow Transplantation (BMT) Unit and the Departments of Pathology and Experimental Medicine, Institute of Medical Pathology, University of Parma; the Division of Oncohematology, Ospedale di Rimini, Rimini; the Department of Hematology, Ospedale Regionale, Bolzano; the Department of Hematology, Spedali Civili, Brescia, Italy; and INSERM U463, Insitut de Biologie, Nantes, France 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Angiopoietin expression in multiple myeloma William T. Bellamy Blood 2003 102: 417-418. [Full Text] [PDF] This article has been cited by other articles: K. Anargyrou, E. Terpos, T. P. Vassilakopoulos, A. Pouli, S. Sachanas, T. Tzenou, S. Masouridis, D. Christoulas, M. K. Angelopoulou, E. M. Dimitriadou, et al. Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib Haematologica, March 1, 2008; 93(3): 451 - 454. [Abstract] [Full Text] [PDF] S. Colla, S. Tagliaferri, F. Morandi, P. Lunghi, G. Donofrio, D. Martorana, C. Mancini, M. Lazzaretti, L. Mazzera, L. Ravanetti, et al. The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) regulates the production of proangiogenic molecules by myeloma cells and suppresses hypoxia-inducible factor-1 {alpha} (HIF-1{alpha}) activity: involvement in myeloma-induced angiogenesis Blood, December 15, 2007; 110(13): 4464 - 4475. [Abstract] [Full Text] [PDF] Y. Tanaka, M. Abe, M. Hiasa, A. Oda, H. Amou, A. Nakano, K. Takeuchi, K. Kitazoe, S. Kido, D. Inoue, et al. Myeloma Cell-Osteoclast Interaction Enhances Angiogenesis Together with Bone Resorption: A Role for Vascular Endothelial Cell Growth Factor and Osteopontin Clin. Cancer Res., February 1, 2007; 13(3): 816 - 823. [Abstract] [Full Text] [PDF] K. E. Fathers, C. M. Stone, K. Minhas, J. J.A. Marriott, J. D. Greenwood, D. J. Dumont, and B. L. Coomber Heterogeneity of Tie2 Expression in Tumor Microcirculation: Influence of Cancer Type, Implantation Site, and Response to Therapy Am. J. Pathol., December 1, 2005; 167(6): 1753 - 1762. [Abstract] [Full Text] [PDF] S. Kanda, Y. Miyata, Y. Mochizuki, T. Matsuyama, and H. Kanetake Angiopoietin 1 Is Mitogenic for Cultured Endothelial Cells Cancer Res., August 1, 2005; 65(15): 6820 - 6827. [Abstract] [Full Text] [PDF] H. Zhang, V. Vakil, M. Braunstein, E. L. P. Smith, J. Maroney, L. Chen, K. Dai, J. R. Berenson, M. M. Hussain, U. Klueppelberg, et al. Circulating endothelial progenitor cells in multiple myeloma: implications and significance Blood, April 15, 2005; 105(8): 3286 - 3294. [Abstract] [Full Text] [PDF] C. Lemieux, R. Maliba, J. Favier, J.-F. Theoret, Y. Merhi, and M. G. Sirois Angiopoietins can directly activate endothelial cells and neutrophils to promote proinflammatory responses Blood, February 15, 2005; 105(4): 1523 - 1530. [Abstract] [Full Text] [PDF] S.A. Schey, P. Fields, J.B. Bartlett, I.A. Clarke, G. Ashan, R.D. Knight, M. Streetly, and A.G. Dalgleish Phase I Study of an Immunomodulatory Thalidomide Analog, CC-4047, in Relapsed or Refractory Multiple Myeloma J. Clin. Oncol., August 15, 2004; 22(16): 3269 - 3276. [Abstract] [Full Text] [PDF] S. Kumar, T. E. Witzig, M. Timm, J. Haug, L. Wellik, T. K. Kimlinger, P. R. Greipp, and S. V. Rajkumar Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression Blood, August 15, 2004; 104(4): 1159 - 1165. [Abstract] [Full Text] [PDF] K. Asosingh, H. De Raeve, E. Menu, I. Van Riet, E. Van Marck, B. Van Camp, and K. Vanderkerken Angiogenic switch during 5T2MM murine myeloma tumorigenesis: role of CD45 heterogeneity Blood, April 15, 2004; 103(8): 3131 - 3137. [Abstract] [Full Text] [PDF] S.-Y. Huang, H.-F. Tien, F.-H. Su, and S.-M. Hsu Nonirradiated NOD/SCID-Human Chimeric Animal Model for Primary Human Multiple Myeloma: A Potential in Vivo Culture System Am. J. Pathol., February 1, 2004; 164(2): 747 - 756. [Abstract] [Full Text] [PDF] A. Vacca, R. Ria, F. Semeraro, F. Merchionne, M. Coluccia, A. Boccarelli, C. Scavelli, B. Nico, A. Gernone, F. Battelli, et al. Endothelial cells in the bone marrow of patients with multiple myeloma Blood, November 1, 2003; 102(9): 3340 - 3348. [Abstract] [Full Text] [PDF] S. Colla, F. Morandi, M. Lazzaretti, P. Polistena, M. Svaldi, P. Coser, S. Bonomini, M. Hojden, E. Martella, T. Chisesi, et al. Do human myeloma cells directly produce basic FGF? Blood, October 15, 2003; 102(8): 3071 - 3073. [Full Text] [PDF]

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