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Blood, 2 July 2009, Vol. 114, No. 1, pp. 128-143. Prepublished online as a Blood First Edition Paper on March 18, 2009; DOI 10.1182/blood-2008-10-184226. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-10-184226v1 114/1/128    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 Google Scholar Articles by Hose, D. Articles by Möhler, T. PubMed PubMed Citation Articles by Hose, D. Articles by Möhler, T. Related Collections Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Induction of angiogenesis by normal and malignant plasma cells Dirk Hose1,2, Jérôme Moreaux3,4, Tobias Meissner1, Anja Seckinger1, Hartmut Goldschmidt1,2, Axel Benner5, Karène Mahtouk3,4, Jens Hillengass1,6, Thierry Rème3,4, John De Vos3,4, Michael Hundemer1, Maud Condomines3,4, Uta Bertsch1, Jean-François Rossi3,4, Anna Jauch7, Bernard Klein3,4, and Thomas Möhler1,2 1 Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany; 2 Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany; 3 Centre Hospitalier Universitaire Montpellier, Institute for Research in Biotherapy, Hôpital Saint-Eloi, Montpellier, France; 4 Inserm U847, Montpellier, France; 5 Abteilung für Biostatistik and 6 Abteilung für Radiologie, Deutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany; and 7 Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Germany Abundant bone marrow angiogenesis is present in almost all myeloma patients requiring therapy and correlated to treatment response and survival. We assessed the expression of 402 angiogenesis-associated genes by Affymetrix DNA microarrays in 466 samples, including CD138-purified myeloma cells (MMCs) from 300 previously untreated patients, in vivo microcirculation by dynamic contrast-enhanced magnetic resonance imaging, and in vitro angiogenesis (AngioKit-assay). Normal bone marrow plasma cells (BMPCs) express a median of 39 proangiogenic (eg, VEGFA, ADM, IGF-1) and 28 antiangiogenic genes (eg, TIMP1, TIMP2). Supernatants of BMPCs unlike those of memory B cells induce angiogenesis in vitro. MMCs do not show a significantly higher median number of expressed proangiogenic (45) or antiangiogenic (31) genes, but 97% of MMC samples aberrantly express at least one of the angiogenic factors HGF, IL-15, ANG, APRIL, CTGF, or TGFA. Supernatants of MMCs and human myeloma cell lines induce significantly higher in vitro angiogenesis compared with BMPCs. In conclusion, BMPCs express a surplus of proangiogenic over antiangiogenic genes transmitting to the ability to induce in vitro angiogenesis. Aberrant expression of proangiogenic and down-regulation of antiangiogenic genes by MMCs further increases the angiogenic stimulus, together leading to bone marrow angiogenesis at various degrees in all myeloma patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Burger, P. Ghia, A. Rosenwald, and F. Caligaris-Cappio The microenvironment in mature B-cell malignancies: a target for new treatment strategies Blood, October 15, 2009; 114(16): 3367 - 3375. [Abstract] [Full Text] [PDF]

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