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

E. Ferretti, C. Tripodo, G. Pagnan, C. Guarnotta, D. Marimpietri, M. V. Corrias, D. Ribatti, S. Zupo, G. Fraternali-Orcioni, J. L. Ravetti, V. Pistoia, A. Corcione

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)958-967
Number of pages10
JournalLeukemia
Volume29
Issue number4
DOIs
Publication statusPublished - Apr 15 2015

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Follicular Lymphoma
Interleukins
Growth
Neoplasms
Germinal Center
B-Lymphocytes
Protein Isoforms
Oncostatin M Receptors
Cell-Derived Microparticles
Interleukin Receptors
Transcription Factor 3
STAT1 Transcription Factor
Cutaneous T-Cell Lymphoma
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
B-Cell Lymphoma

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine
  • Medicine(all)

Cite this

The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma. / Ferretti, E.; Tripodo, C.; Pagnan, G.; Guarnotta, C.; Marimpietri, D.; Corrias, M. V.; Ribatti, D.; Zupo, S.; Fraternali-Orcioni, G.; Ravetti, J. L.; Pistoia, V.; Corcione, A.

In: Leukemia, Vol. 29, No. 4, 15.04.2015, p. 958-967.

Research output: Contribution to journalArticle

Ferretti, E, Tripodo, C, Pagnan, G, Guarnotta, C, Marimpietri, D, Corrias, MV, Ribatti, D, Zupo, S, Fraternali-Orcioni, G, Ravetti, JL, Pistoia, V & Corcione, A 2015, 'The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma', Leukemia, vol. 29, no. 4, pp. 958-967. https://doi.org/10.1038/leu.2014.291
Ferretti, E. ; Tripodo, C. ; Pagnan, G. ; Guarnotta, C. ; Marimpietri, D. ; Corrias, M. V. ; Ribatti, D. ; Zupo, S. ; Fraternali-Orcioni, G. ; Ravetti, J. L. ; Pistoia, V. ; Corcione, A. / The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma. In: Leukemia. 2015 ; Vol. 29, No. 4. pp. 958-967.
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AU - Ribatti, D.

AU - Zupo, S.

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