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Lymphoma

The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma

Leukemia volume 29, pages 958–967 (2015)Cite this article

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Abstract

Interleukin (IL)-31A binds to an heterodimer composed of IL-31 receptor A (IL-31RA) and Oncostatin M Receptor (OSMR). The IL-31/IL-31R complex is involved in the pathogenesis of various skin diseases, including cutaneous T-cell lymphoma. No information is available on the relations between the IL-31/IL-31R complex and B-cell lymphoma. Here we have addressed this issue in follicular lymphoma (FL), a prototypic germinal center(GC)-derived B-cell malignancy. IL-31 enhanced primary FL cell proliferation through IL-31R-driven signal transducer and activator of transcription factor 1/3 (STAT1/3), extracellular signal–regulated kinase 1/2 (ERK1/2) and Akt phosphorylation. In contrast, GC B cells did not signal to IL-31 in spite of IL-31R expression. GC B cells expressed predominantly the inhibitory short IL-31RA isoform, whereas FL cells expressed predominantly the long signaling isoform. Moreover, GC B cells lacked expression of other IL-31RA isoforms potentially involved in the signaling pathway. IL-31 protein expression was significantly higher in surface membrane than in cytosol of both FL and GC B cells. IL-31 was detected in plasma membrane microvesicles from both cell types but not released in soluble form in culture supernatants. IL-31 and IL-31RA expression was higher in lymph nodes from FL patients with grade IIIa compared with grade I/II, suggesting a paracrine and/or autocrine role of IL-31/IL-31RA complex in tumor progression through microvesicle shedding.

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Acknowledgements

This work was supported by grants from Associazione Italiana Ricerca Cancro (A.I.R.C.), Milano, Italy to VP (No. 13003), from Cinque per mille IRPEF–Finanziamento Ricerca Sanitaria and from Ricerca Corrente Ministeriale. EF is a recipient of a Fondazione Umberto Veronesi fellowship. We thank Dr Francesco Bertoni for help in discussion. European Union Seventh Frame Programme (FP7/2007-2013) under grant agreement N° 278570 to DR.

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  1. V Pistoia and A Corcione: These two authors shared last authorship.

Authors and Affiliations

  1. Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy

    E Ferretti, G Pagnan, D Marimpietri, M V Corrias, V Pistoia & A Corcione

  2. Department of Health Science, Tumor Immunology Unit, Human Pathology Section, University of Palermo, Palermo, Italy

    C Tripodo & C Guarnotta

  3. Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari Medical School, Bari and National Cancer Institute "Giovanni Paolo II", Bari, Italy

    D Ribatti

  4. Laboratory of Diagnostics of Lymphoproliferative Disorders, National Cancer Research Institute, Genova, Italy

    S Zupo

  5. Unit of Pathology, IRCCS Azienda Ospedaliera Universitaria San Martino—IST—Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy

    G Fraternali-Orcioni & J L Ravetti

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Correspondence to A Corcione.

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Ferretti, E., Tripodo, C., Pagnan, G. et al. The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma. Leukemia 29, 958–967 (2015). https://doi.org/10.1038/leu.2014.291

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