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

Author

Listed:
  • 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
    Asia University)

  • Ning-Sun Yang

    (Agricultural Biotechnology Research Center, Academia Sinica)

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.

Suggested Citation

  • Shu-Yi Yin & Feng-Yin Jian & Yung-Hsiang Chen & Shih-Chang Chien & Mao-Chih Hsieh & Pei-Wen Hsiao & Wen-Hwa Lee & Yueh-Hsiung Kuo & Ning-Sun Yang, 2016. "Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11311
    DOI: 10.1038/ncomms11311
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