Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis

Shu-Yi Yin, Feng-Yin Jian, Yung-Hsiang Chen, Shih-Chang Chien, Mao-Chih Hsieh, Pei-Wen Hsiao, Wen-Hwa Lee, Yueh-Hsiung Kuo () and Ning-Sun Yang ()
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Shu-Yi Yin: Agricultural Biotechnology Research Center, Academia Sinica
Feng-Yin Jian: Agricultural Biotechnology Research Center, Academia Sinica
Yung-Hsiang Chen: Agricultural Biotechnology Research Center, Academia Sinica
Shih-Chang Chien: The Experimental Forest Management Office, National Chung Hsing University
Mao-Chih Hsieh: Wan-Fang Hospital
Pei-Wen Hsiao: Agricultural Biotechnology Research Center, Academia Sinica
Wen-Hwa Lee: China Medical University
Yueh-Hsiung Kuo: China Medical University
Ning-Sun Yang: Agricultural Biotechnology Research Center, Academia Sinica

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Tumour-associated fibroblasts (TAFs), as a functionally supportive microenvironment, play an essential role in tumour progression. Here we investigate the role of IL-25, an endogenous anticancer factor secreted from TAFs, in suppression of mouse 4T1 mammary tumour metastasis. We show that a synthetic dihydrobenzofuran lignan (Q2-3), the dimerization product of plant caffeic acid methyl ester, suppresses 4T1 metastasis by increasing fibroblastic IL-25 activity. The secretion of IL-25 from treated human or mouse fibroblasts is enhanced in vitro, and this activity confers a strong suppressive effect on growth activity of test carcinoma cells. Subsequent in vivo experiments showed that the anti-metastatic effects of Q2-3 on 4T1 and human MDA-MD-231 tumour cells are additive when employed in combination with the clinically used drug, docetaxel. Altogether, our findings reveal that the release of IL-25 from TAFs may serve as a check point for control of mammary tumour metastasis and that phytochemical Q2-3 can efficiently promote such anticancer activities.

Date: 2016
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DOI: 10.1038/ncomms11311

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