title: The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma.
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.
authors.affiliation: Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ferretti
authors.affiliation: Tumor Immunology Unit, Department of Health Science, Human Pathology Section, University of Palermo, Palermo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tripodo
authors.affiliation: Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pagnan
authors.affiliation: Tumor Immunology Unit, Department of Health Science, Human Pathology Section, University of Palermo, Palermo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Guarnotta
authors.affiliation: Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Marimpietri
authors.affiliation: Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: M V
authors.initials: MV
authors.lastname: Corrias
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari Medical School, Bari and National Cancer Institute "Giovanni Paolo II", Bari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Ribatti
authors.affiliation: Laboratory of Diagnostics of Lymphoproliferative Disorders, National Cancer Research Institute, Genova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Zupo
authors.affiliation: Unit of Pathology, IRCCS Azienda Ospedaliera Universitaria San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Fraternali-Orcioni
authors.affiliation: Unit of Pathology, IRCCS Azienda Ospedaliera Universitaria San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: J L
authors.initials: JL
authors.lastname: Ravetti
authors.affiliation: Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Pistoia
authors.affiliation: Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Corcione
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D055252:Cell-Derived Microparticles / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018858:Germinal Center / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D060787:Neoplasm Grading; D010766:Phosphorylation; D061251:Primary Cell Culture; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C502187:IL31 protein, human; C502188:IL31RA protein, human; D007378:Interleukins; D020033:Protein Isoforms; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3