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However, it is still unclear how tumour cells contribute to this process. Here, we observed that paclitaxel and carboplatin accelerated lung metastasis in tumour\u2010bearing mice, while doxorubicin and fluorouracil did not. Mechanistically, paclitaxel and carboplatin induced similar changes in cytokine and angiogenic factors. Increased levels of <jats:styled-content style=\"fixed-case\">CXCR2<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">CXCR4<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">S1P<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">S1PR1<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">PlGF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PDGF\u2010BB<\/jats:styled-content> were identified in the serum or primary tumour tissues of tumour\u2010bearing mice treated by paclitaxel. The serum levels of <jats:styled-content style=\"fixed-case\">CXCL1<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PDGF\u2010BB<\/jats:styled-content> and the tissue level of <jats:styled-content style=\"fixed-case\">CXCR4<\/jats:styled-content> were also elevated by carboplatin. On the other hand, doxorubicin and fluorouracil did not induce such changes. The chemotherapy\u2010induced cytokine and angiogenic factor changes were also confirmed in gene expression datasets from human patients following chemotherapy treatment. These chemotherapy\u2010enhanced cytokines and angiogenic factors further induced angiogenesis, destabilized vascular integrity, recruited <jats:styled-content style=\"fixed-case\">BMDCs<\/jats:styled-content> to metastatic organs and mediated the proliferation, migration and epithelial\u2010to\u2010mesenchymal transition of tumour cells. Interestingly, inhibitors of these factors counteracted chemotherapy\u2010enhanced metastasis in both tumour\u2010bearing mice and normal mice injected intravenously with <jats:styled-content style=\"fixed-case\">B16F10\u2013GFP<\/jats:styled-content> cells. In particular, blockade of the <jats:styled-content style=\"fixed-case\">SDF<\/jats:styled-content>\u20101\u03b1\u2013<jats:styled-content style=\"fixed-case\">CXCR4<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">S1P\u2013S1PR1<\/jats:styled-content> axes not only compromised chemotherapy\u2010induced metastasis but also prolonged the median survival time by 33.9% and 40.3%, respectively. The current study delineates the mechanism of chemotherapy\u2010induced metastasis and provides novel therapeutic strategies to counterbalance pro\u2010metastatic effects of chemo\u2010drugs via combination treatment with anti\u2010cytokine\/anti\u2010angiogenic therapy. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4564","type":"journal-article","created":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T07:10:31Z","timestamp":1432019431000},"page":"190-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Specific chemotherapeutic agents induce metastatic behaviour through stromal\u2010 and tumour\u2010derived cytokine and angiogenic factor signalling"],"prefix":"10.1002","volume":"237","author":[{"given":"Guanghua","family":"Liu","sequence":"first","affiliation":[{"name":"The National Engineering Laboratory for Anti\u2010Tumour Protein Therapeutics Tsinghua University  Beijing People's Republic of China"},{"name":"Beijing Key Laboratory for Protein Therapeutics Tsinghua University  Beijing People's Republic of China"},{"name":"Cancer Biology Laboratory, School of Life Sciences Tsinghua University  Beijing People's Republic of 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