Interleukin-27 acts as multifunctional antitumor agent in multiple myeloma

Claudia Cocco, Nicola Giuliani, Emma Di Carlo, Emanuela Ognio, Paola Storti, Manuela Abeltino, Carlo Sorrentino, Maurilio Ponzoni, Domenico Ribatti, Irma Airoldi

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Abstract

Purpose: Multiple myeloma (MM) derives from plasmablast/plasma cells that accumulate in the bone marrow. Different microenvironmental factors may promote metastatic dissemination especially to the skeleton, causing bone destruction. The balance between osteoclast and osteoblast activity represents a critical issue in bone remodeling. Thus, we investigated whether interluekin-27 (IL-27) may function as an antitumor agent by acting directly on MM cells and/or on osteoclasts/osteoblasts. Experimental Design: The IL-27 direct antitumor activity on MM cells was investigated in terms of angiogenesis, proliferation, apoptosis, and chemotaxis. The IL-27 activity on osteoclast/osteoblast differentiation and function was also tested. In vivo studies were done using severe combined immunodeficient/ nonobese diabetic mice injected with MM cell lines. Tumors from IL-27- and PBS-treated mice were analyzed by immunohistochemistry and PCR array. Results: We showed that IL-27 (a) strongly inhibited tumor growth of primary MM cells and MM cell lines through inhibition of angiogenesis, (b) inhibited osteoclast differentiation and activity and induced osteoblast proliferation, and (c) damped in vivo tumorigenicity of human MM cell lines through inhibition of angiogenesis. Conclusions: These findings show that IL-27 may represent a novel therapeutic agent capable of inhibiting directly MM cell growth as well as osteoclast differentiation and activity.

Original languageEnglish
Pages (from-to)4188-4197
Number of pages10
JournalClinical Cancer Research
Volume16
Issue number16
DOIs
Publication statusPublished - Aug 15 2010

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cocco, C., Giuliani, N., Di Carlo, E., Ognio, E., Storti, P., Abeltino, M., Sorrentino, C., Ponzoni, M., Ribatti, D., & Airoldi, I. (2010). Interleukin-27 acts as multifunctional antitumor agent in multiple myeloma. Clinical Cancer Research, 16(16), 4188-4197. https://doi.org/10.1158/1078-0432.CCR-10-0173