title: Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis.
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.
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Yin
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Feng-Yin
authors.initials: FY
authors.lastname: Jian
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.affiliation: The Experimental Forest Management Office, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Chien
authors.affiliation: Department of Surgery, Wan-Fang Hospital, Taipei 116, Taiwan.
authors.forename: Mao-Chih
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Hsiao
authors.affiliation: China Medical University, Taichung 404, Taiwan.
authors.forename: Wen-Hwa
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan.|Department of Biotechnology, Asia University, Taichung 413, Taiwan.
authors.forename: Yueh-Hsiung
authors.identifier: http://orcid.org/0000-0001-5935-6755
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Ning-Sun
authors.initials: NS
authors.lastname: Yang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007378:Interleukins; D017705:Lignans; C442281:Mydgf protein, mouse