IL-37 mediates the antitumor activity in renal cell carcinoma

• Published in: Medical oncology (Northwood, London, England) Vol. 32; no. 11; p. 250
• Main Authors: Jiang, Yazhuo, Wang, Yili, Liang, Liang, Gao, Yang, Chen, Juan, Sun, Yi, Cheng, Yongyi, Xu, Yonggang
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2015; Springer Nature B.V
• Subjects: Animals; Biomarkers, Tumor - blood; Carcinoma, Renal Cell - blood; Carcinoma, Renal Cell - drug therapy; Cell Line, Tumor; Cohort Studies; Dose-Response Relationship, Drug; Double-Blind Method; Hematology; Humans; Interleukin-1 - blood; Interleukin-1 - therapeutic use; Internal Medicine; Kidney Neoplasms - blood; Kidney Neoplasms - drug therapy; Male; Medicine; Medicine & Public Health; Mice; Mice, SCID; Oncology; Original Paper; Pathology; Prospective Studies; Xenograft Model Antitumor Assays - methods; IL-37; IL-6/STAT3 signaling; Renal cell carcinoma; Antitumor
• ISSN: 1357-0560; 1559-131X; 1559-131X
• DOI: 10.1007/s12032-015-0695-7

Interleukin (IL)-37 is a natural suppressor of innate inflammatory and immune responses. IL-37 plays an important role in renal function and antitumor activity. The aim of this study was to investigate the role of IL-37 in renal cell carcinoma (Rcc). Serum IL-37 levels in 120 Rcc patients and 50 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). The Rcc cell lines A498 and Caki-1 were cultured with 0–100 ng/mL of recombinant human IL-37 protein (rhIL-37). Cancer cells were transfected with or without pcDNA3.1-IL-6 to alter IL-6 expression. Cell migration, proliferation, and apoptosis were tested by wound-healing assay, MTT, and flow cytometry, respectively. Levels of IL-6, pSTAT3 Y705, Bcl-2, cyclin D1, and HIF-1α were detected by qRT-PCR, ELISA, or western blot. Additionally, therapeutic effect of rhIL-37 was also confirmed in SCID mice. The expression of IL-37 was decreased in Rcc patients and was negatively correlated with tumor progression. In vitro, IL-37 markedly inhibited the migration and proliferation, and promoted apoptosis in Rcc cells. Furthermore, the expressions of IL-6, pSTAT3 Y705, HIF-1α, Bcl-2, and cyclin D1 were decreased by IL-37. However, these effects were reversed by the transfection of pcDNA3.1-IL-6. In vivo, tumor growth and gene expressions of IL-6 and HIF-1α were suppressed by IL-37. In conclusion, IL-37 might serve as a novel tumor suppressor in Rcc and exert its antitumor activity through inhibiting IL-6/STAT3 signaling.