Interleukin-27 Acts as Multifunctional Antitumor Agent in Multiple Myeloma

Download pose: Multiple myeloma (MM) derives from plasmablast/plasma cells that accumulate in the bone w. Different microenvironmental factors may promote metastatic dissemination especially to the on, causing bone destruction. The balance between osteoclast and osteoblast activity represents a l issue in bone remodeling. Thus, we investigated whether interluekin-27 (IL-27) may function as titumor agent by acting directly on MM cells and/or on osteoclasts/osteoblasts. erimental Design: The IL-27 direct antitumor activity on MM cells was investigated in terms of genesis, proliferation, apoptosis, and chemotaxis. The IL-27 activity on osteoclast/osteoblast differion and function was also tested. In vivo studies were done using severe combined immunodefinonobese diabetic mice injected with MM cell lines. Tumors from IL-27– and PBS-treated mice nalyzed by immunohistochemistry and PCR array. ults: We showed that IL-27 (a) strongly inhibited tumor growth of primary MM cells and MM cell hrough inhibition of angiogenesis, (b) inhibited osteoclast differentiation and activity and induced last proliferation, and (c) damped in vivo tumorigenicity of human MM cell lines through inhibif angiogenesis. clusions: These findings show that IL-27 may represent a novel therapeutic agent capable of Con inhibiting directly MM cell growth as well as osteoclast differentiation and activity. Clin Cancer Res;

[1]  D. Ribatti,et al.  IL-12 Can Target Human Lung Adenocarcinoma Cells and Normal Bronchial Epithelial Cells Surrounding Tumor Lesions , 2009, PloS one.

[2]  T. Yoshimoto,et al.  Effects of IL-23 and IL-27 on osteoblasts and osteoclasts: inhibitory effects on osteoclast differentiation , 2007, Journal of Bone and Mineral Metabolism.

[3]  M. Neurath,et al.  IL‐27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1 , 2007, European journal of immunology.

[4]  D. Ribatti,et al.  Endogenous IL-12 triggers an antiangiogenic program in melanoma cells , 2007, Proceedings of the National Academy of Sciences.

[5]  L. Hennighausen,et al.  Interleukin 27 negatively regulates the development of interleukin 17–producing T helper cells during chronic inflammation of the central nervous system , 2006, Nature Immunology.

[6]  R. Kastelein,et al.  Differential effects of IL-27 on human B cell subsets , 2006, The Journal of Immunology.

[7]  D. Danilenko,et al.  Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cells , 2006, Nature Immunology.

[8]  D. Ribatti,et al.  Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma , 2006, Oncogene.

[9]  H. Nagai,et al.  Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma. , 2006, Cancer research.

[10]  D. Ribatti,et al.  Bone marrow angiogenesis in multiple myeloma , 2006, Leukemia.

[11]  S. Khader,et al.  IL-27 Signaling Compromises Control of Bacterial Growth in Mycobacteria-Infected Mice1 , 2004, The Journal of Immunology.

[12]  S. Colla,et al.  Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. , 2004, Blood.

[13]  G. Wu,et al.  The IL-27 Receptor (WSX-1) Is an Inhibitor of Innate and Adaptive Elements of Type 2 Immunity1 , 2004, The Journal of Immunology.

[14]  C. Hunter,et al.  Biology of recently discovered cytokines: Discerning the pro- and anti-inflammatory properties of interleukin-27 , 2004, Arthritis research & therapy.

[15]  C. Hunter,et al.  Understanding the Pro- and Anti-Inflammatory Properties of IL-271 , 2004, The Journal of Immunology.

[16]  Oswald Wagner,et al.  Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas. , 2004, The New England journal of medicine.

[17]  Maria Laura Belladonna,et al.  Potent Antitumor Activity of Interleukin-27 , 2004, Cancer Research.

[18]  T. Mak,et al.  WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production. , 2003, Immunity.

[19]  R. Bataille,et al.  Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. , 2002, Blood.

[20]  T. Mcclanahan,et al.  IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. , 2002, Immunity.

[21]  F.J. Sauvage,et al.  Development of Th1-type immune responses requires the type I cytokine receptor TCCR , 2000, Nature.

[22]  P. Meltzer,et al.  Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. , 1999, The American journal of pathology.

[23]  D. Ribatti,et al.  Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. , 1999, Blood.

[24]  A Vacca,et al.  New model for the study of angiogenesis and antiangiogenesis in the chick embryo chorioallantoic membrane: the gelatin sponge/chorioallantoic membrane assay. , 1997, Journal of vascular research.

[25]  J. Kanis,et al.  Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption , 1992, European journal of haematology.

[26]  T. Spelsberg,et al.  Evidence for interleukin‐1β production by cultured normal human osteoblast‐like cells , 1991 .

[27]  R. Bataille,et al.  Mechanisms of bone destruction in multiple myeloma: the importance of an unbalanced process in determining the severity of lytic bone disease. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  S. Salmon,et al.  A clinical staging system for multiple myeloma correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival , 1975, Cancer.

[29]  古川 満 IL-27 abrogates receptor activator of NF-κB ligand-mediated osteoclastogenesis of human granulocyte-macrophage colony-forming unit cells through STAT1-dependent inhibition of c-Fos , 2010 .

[30]  R. Arceci Tumor Origin of Endothelial Cells in Human Neuroblastoma , 2008 .

[31]  Thomas D. Schmittgen,et al.  Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2 2 DD C T Method , 2022 .