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Review
, 52 (3), 165-174

Interleukin-32: Frenemy in Cancer?

Affiliations
Review

Interleukin-32: Frenemy in Cancer?

Sora Han et al. BMB Rep.

Abstract

Interleukin-32 (IL-32) was originally identified in natural killer (NK) cells activated by IL-2 in 1992. Thus, it was named NK cell transcript 4 (NK4) because of its unknown function at that time. The function of IL-32 has been elucidated over the last decade. IL-32 is primarily considered to be a booster of inflammatory reactions because it is induced by proinflammatory cytokines and stimulates the production of those cytokines and vice versa. Therefore, many studies have been devoted to studying the roles of IL-32 in inflammationassociated cancers, including gastric, colon cancer, and hepatocellular carcinoma. At the same time, roles of IL-32 have also been discovered in other cancers. Collectively, IL-32 fosters the tumor progression by nuclear factor-κB (NF-κB)-mediated cytokines and metalloproteinase production, as well as stimulation of differentiation into immunosuppressive cell types in some cancer types. However, it is also able to induce tumor cell apoptosis and enhance NK and cytotoxic T cell sensitivity in other cancer types. In this review, we will address the function of each IL-32 isoform in different cancer types studied to date, and suggest further strategies to comprehensively elucidate the roles of IL-32 in a contextdependent manner. [BMB Reports 2019; 52(3): 165-174].

Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicting interests.

Figures

Fig. 1
Fig. 1
Biological functions of IL-32 in inflammatory tumors. Different colors indicate each cancer type and cancer type specific signaling pathway. AOM: azoxymethane, ROS: reactive oxygen species, JNK: c-Jun N-terminal kinases, NF-κB: nuclear factor kappa B, TIMP: tissue inhibitors of metalloproteinase, MMP: matrix metalloproteinase, H. pylori: Helicobacter pylori, cagPAI: cytotoxin-associated gene pathogenicity island, HBV: hepatitis B virus, HCV: hepatitis C virus, VEGF: vascular endothelial growth factor, CXCL: C-X-C motif chemokine, CCL: C-C motif chemokine ligands, TNF-α: tumor necrosis factor α, PI3K: phosphoinositide 3-kinase, AP-1: activated protein 1.
Fig. 2
Fig. 2
Biological functions of IL-32 in non-inflammatory tumors. Different colors indicate each cancer type and cancer type specific signaling pathway. H. pylori: Helicobacter pylori, COX2: cyclooxygenase 2, ROS: reactive oxygen species, HPV E7: human papillomavirus E7 oncoprotein, PARP: poly ADP-ribose polymerase, VEGF: vascular endothelial growth factor, pSTAT3: phosphorylated signal transducer and activator of transcription 3, PKCδ: protein kinase C δ.
Fig. 3
Fig. 3
IL-32 affects both tumor growth and death by modulating immune cells. (A) IL-32 stimulates tumor and NK cells to facilitate tumor cell killing. Expression levels of NK cell target proteins, including FAS and ULBP are upregulated in IL-32α-expressing CML (upper). IL-32-expressing NK cells secrete the ligands for DR3 and TNFR2, DR3 and TNF, respectively (bottom). (B) IL-32-expressing tumor cells recruit anti-tumoral NK cells and CTLs, while IL-32 also stimulates the differentiation of immunosuppressive CD11c+ mDC and CD163+CD68+ MΦ. FASL: Fas ligand, ULBP2: UL16-binding protein 2, NKG2D: natural killer group 2D, CML: chronic myeloid leukemia, NK cell: natural killer cell, TNFR2: tumor necrosis factor receptor 2, DR3: death receptor 3, CTL: cytotoxic T lymphocytes, MΦ: macrophages, mDC: mature dendritic cells.

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