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Blood First Edition Paper, prepublished online May 12, 2008; DOI 10.1182/blood-2008-02-139378. This Article Full Text (PDF) 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 CrossRef Google Scholar Articles by Airoldi, I. Articles by Pistoia, V. PubMed PubMed Citation Articles by Airoldi, I. Articles by Pistoia, V. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 14, 2008 Accepted March 30, 2008 Constitutive expression of IL-12RB2 on human multiple myeloma cells delineates a novel therapeutic target Irma Airoldi*, Claudia Cocco, Nicola Giuliani, Marina Ferrarini, Simona Colla, Emanuela Ognio, Giuseppe Taverniti, Emma Di Carlo, Giovanna Cutrona, Vittorio Perfetti, Vittorio Rizzoli, Domenico Ribatti, and Vito Pistoia Department of Experimental and Laboratory Medicine, G. Gaslini Institute, Genova, Italy Laboratory of Oncology, G. Gaslini Institute, Genova, Italy Hematology and BMT Center, Department of Internal Medicine and Biomedical Science, University of Parma, Parma, Italy Laboratory of Tumor Immunology and Department of Oncology, Istituto Scientifico H.San Raffaele, Milano, Italy Hematology and BMT Center, Department of Internal Medicine and Biomedical Science, University di Parma, Parma, Italy Animal Model Facility, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy Department of Oncology and Neurosciences, "G. d'Annunzio" University and Ce.S.I. Aging Research Center, Chieti, Italy Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy Internal Medicine and Medical Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy Department of Human Anatomy and Histology, University of Bari, Bari, Italy * Corresponding author; email: irmaairoldi{at}ospedale-gaslini.ge.it. The IL-12 receptor(R)B2 gene acts as tumor suppressor in human acute and chronic B cell leukemias/lymphomas and IL-12rb2 deficient mice develop spontaneously localized plasmacytomas. With this background, we have investigated the role of IL-12RB2 in multiple myeloma (MM) pathogenesis. Here we show that i) IL12R2 was expressed in primary MM cells, but downregulated in comparison with normal polyclonal plasmablastic cells (PPC) and plasma cells (PC). IL-6 dampened IL-12R2 expression on PPC and MM cells, and ii) IL-12 reduced the pro-angiogenic activity of primary MM cells in vitro and decreased significantly (P=0.0001) the tumorigenicity of the NCI-H929 cell line in SCID/NOD mice by inhibiting cell proliferation and angiogenesis. The latter phenomenon was found to depend on abolished expression of a wide panel of pro-angiogenic genes and up-regulated expression of the antiangiogenic genes IFN-, IFN-, platelet factor-4 and TIMP-2. Inhibition of the angiogenic potential of primary MM cells was related to down-regulated expression of the pro-angiogenic genes CCL11, vascular endothelial-cadherin, CD13 and AKT and to up-regulation of an IFN- related anti-angiogenic pathway. Thus, IL-12R2 restrains directly MM cell growth, and targeting of IL-12 to tumor cells holds promise as new therapeutic strategy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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