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Blood, 1 August 2008, Vol. 112, No. 3, pp. 750-759. Prepublished online as a Blood First Edition Paper on May 12, 2008; DOI 10.1182/blood-2008-02-139378. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-02-139378v1 112/3/750    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Airoldi, I. Articles by Pistoia, V. Search for Related Content PubMed PubMed Citation Articles by Airoldi, I. Articles by Pistoia, V. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Constitutive expression of IL-12Rβ2 on human multiple myeloma cells delineates a novel therapeutic target Irma Airoldi1,*, Claudia Cocco2,*, Nicola Giuliani3, Marina Ferrarini4, Simona Colla3, Emanuela Ognio5, Giuseppe Taverniti5, Emma Di Carlo6, Giovanna Cutrona7, Vittorio Perfetti8, Vittorio Rizzoli3, Domenico Ribatti9, and Vito Pistoia2 1 Department of Experimental and Laboratory Medicine and 2 Laboratory of Oncology, G. Gaslini Institute, Genova; 3 Hematology and BMT Center, Department of Internal Medicine and Biomedical Science, University of Parma, Parma; 4 Laboratory of Tumor Immunology and Department of Oncology, Istituto Scientifico H. San Raffaele, Milano; 5 Animal Model Facility, Istituto Nazionale per la Ricerca sul Cancro, Genova; 6 Department of Oncology and Neurosciences, G. d'Annunzio University and Ce.S.I. Aging Research Center, G. d'Annunzio University Foundation, Chieti; 7 Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, Genova; 8 Internal Medicine and Medical Oncology, IRCCS Policlinico S. Matteo, Pavia; and 9 Department of Human Anatomy and Histology, University of Bari, Bari, Italy The interleukin-12 (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 investigated the role of IL-12Rβ2 in multiple myeloma (MM) pathogenesis. Here we show the following: (1) IL-12Rβ2 was expressed in primary MM cells but down-regulated compared with normal polyclonal plasmablastic cells and plasma cells (PCs). IL-6 dampened IL-12Rβ2 expression on polyclonal plasmablastic cells and MM cells. (2) IL-12 reduced the proangiogenic activity of primary MM cells in vitro and decreased significantly (P = .001) 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 proangiogenic 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 proangiogenic genes CCL11, vascular endothelial-cadherin, CD13, and AKT and to up-regulation of an IFN-–related antiangiogenic pathway. Thus, IL-12Rβ2 directly restrains 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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