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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 (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 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 Hose, D. Articles by Mohler, T. Search for Related Content PubMed PubMed Citation Articles by Hose, D. Articles by Mohler, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 17, 2008 Accepted March 9, 2009 Induction of angiogenesis by normal and malignant plasma cells Dirk Hose*, Jerome Moreaux, Tobias Meissner, Anja Seckinger, Hartmut Goldschmidt, Axel Benner, Karene Mahtouk, Jens Hillengass, Thierry Reme, John De Vos, Michael Hundemer, Maud Condomines, Uta Bertsch, Jean-Francois Rossi, Anna Jauch, Bernard Klein, and Thomas Mohler Medizinische Klinik V, Universitatsklinikum Heidelberg, Heidelberg, Germany CHU Montpellier, Institute for Research in Biotherapy, Hopital Saint-Eloi, Montpellier, France Nationales Centrum fur Tumorerkrankungen, Heidelberg, Germany Abteilung fur Biostatistik, Deutsches Krebsforschungszentrum, Heidelberg, Germany INSERM U847, Montpellier, France Abteilung fur Radiologie, Deutsches Krebforschungszentrum Heidelberg, Heidelberg, Germany Institut fur Humangenetik, Universitatsklinikum Heidelberg, Heidelberg, Germany * Corresponding author; email: dirk.hose{at}med.uni-heidelberg.de. 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 pro- (e.g. VEGFA, ADM, IGF-1) and 28 anti-angiogenic genes (e.g. 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 pro- (45) or anti-angiogenic (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 to BMPCs. In conclusion, BMPCs express a surplus of pro- over anti-angiogenic genes transmitting to the ability to induce in vitro angiogenesis. Aberrant expression of pro- and down-regulation of anti-angiogenic genes by MMCs further increases the angiogenic stimulus, together leading to bone marrow angiogenesis at varying 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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