Original Article

Transfer of the IL-37b gene elicits anti-tumor responses in mice bearing 4T1 breast cancer

Wei-qiang WANG, Dan ZHAO, Yu-shan ZHOU, Xiao-yu HU, Zhi-na SUN, Gang YU, Wan-tong WU, Song CHEN, Jiu-long KUANG, Guo-gang XU, Zhong-chao HAN, Bang-mao WANG, Jing-xian YANG, Xiao-ming FENG
DOI: 10.1038/aps.2015.3

Abstract

Aim: IL-37b has shown anti-cancer activities in addition to its anti-inflammatory properties. In this study, we investigated the effects of IL-37b on breast carcinoma growth in mice and to determine the involvement of T cell activation in the effects.
Methods: IL-37b gene was transferred into mouse breast carcinoma cell line 4T1 (4T1-IL37b cells), the expression of secretory IL-37b by the cells was detected, and the effects of IL-37b expression on the cell proliferation in vitro was evaluated. After injection of 4T1 cells or 4T1-IL37b cells into immunocompetent BALB/c mice, immunodeficient BALB/c nude mice and NOD-SCID mice, the tumor growth and survival rate were measured. The proliferation of T cells in vitro was also detected.
Results: IL-37b was detected in the supernatants of 4T1-IL37b cells with a concentration of 12.02±0.875 ng/mL. IL-37b expression did not affect 4T1 cell proliferation in vitro. BALB/c mice inoculated with 4T1-IL37b cells showed significant retardation of tumor growth. BALB/c mice inoculated with both 4T1 cells and mitomycin C-treated 4T1-IL37b cells also showed significant retardation of tumor growth. But the anti-cancer activity of IL-37b was abrogated in BALB/c nude mice and NOD-SCID mice inoculated with 4T1-IL37b cells. Recombinant IL-37b slightly promoted CD4+ T cell proliferation without affecting CD8+ T cell proliferation.
Conclusion: IL-37b exerts anti-4T1 breast carcinoma effects in vivo by modulating the tumor microenvironment and influencing T cell activation.
Keywords: IL-37b; breast cancer; anti-cancer effect; mitomycin C; T cell; tumor microenvironment

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