Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Airoldi, I. et al.

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,

Constitutive expression of IL-12R beta 2 on human multiple myeloma cells delineates a novel therapeutic target.

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-12R beta 2 in multiple myeloma (MM) pathogenesis. Here we show the following: (1) IL-12R beta 2 was expressed in primary MM cells but down-regulated compared with normal polyclonal plasmablastic cells and plasma cells (PCs). IL-6 dampened IL-12R beta 2 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-gamma, IFN-alpha, 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-gamma-related antiangiogenic pathway. Thus, IL-12R beta 2 directly restrains MM cell growth, and targeting of IL-12 to tumor cells holds promise as new therapeutic strategy.[1]

References

Constitutive expression of IL-12R beta 2 on human multiple myeloma cells delineates a novel therapeutic target. 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. Blood (2008) [Pubmed]

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