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.

中文翻译：

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诱导肿瘤相关成纤维细胞分泌IL-25抑制了乳腺肿瘤的转移。

肿瘤相关的成纤维细胞（TAF），作为功能性支持的微环境，在肿瘤的进展中起着至关重要的作用。在这里，我们研究了IL-25（一种由TAF分泌的内源性抗癌因子）在抑制小鼠4T1乳腺肿瘤转移中的作用。我们表明，合成的二氢苯并呋喃木脂素（Q2-3），植物咖啡酸甲酯的二聚产物，通过增加成纤维细胞IL-25活性来抑制4T1转移。经处理的人或小鼠成纤维细胞的IL-25分泌在体外得到增强，并且这种活性对测试癌细胞的生长活性具有很强的抑制作用。随后的体内实验表明，与临床使用的药物多西他赛联合使用时，Q2-3对4T1和人MDA-MD-231肿瘤细胞的抗转移作用是加和的。