Constitutive expression of IL-12R 22 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, Vito Pistoia

Research output: Contribution to journalArticle

Abstract

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 NCIH929 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-γ, IFN-α, 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-γ-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.

Original languageEnglish
Pages (from-to)750-759
Number of pages10
JournalBlood
Volume112
Issue number3
DOIs
Publication statusPublished - Aug 1 2008

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Airoldi, I., Cocco, C., Giuliani, N., Ferrarini, M., Colla, S., Ognio, E., Taverniti, G., Di Carlo, E., Cutrona, G., Perfetti, V., Rizzoli, V., Ribatti, D., & Pistoia, V. (2008). Constitutive expression of IL-12R 22 on human multiple myeloma cells delineates a novel therapeutic target. Blood, 112(3), 750-759. https://doi.org/10.1182/blood-2008-02-139378