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Evidence is growing that NETs exert manifold functions in infection, immunity and cancer. Recently, NETs have been detected in colorectal cancer (CRC) tissues, but their association with disease progression and putative functional impact on tumourigenesis remained elusive. Using high\u2010resolution stimulated emission depletion (STED) microscopy, we showed that citrullinated histone H3 (H3cit) is sufficient to specifically detect citrullinated NETs in colon cancer tissues. Among other evidence, this was supported by the close association of H3cit with de\u2010condensed extracellular DNA, the hallmark of NETs. Extracellular DNA was reliably differentiated from nuclear condensed DNA by staining with an anti\u2010DNA antibody, providing a novel and valuable tool to detect NETs in formalin\u2010fixed paraffin\u2010embedded tissues. Using these markers, the clinical association of NETs was investigated in a cohort of 85 patients with colon cancer. NETs were frequently detected (37\/85, 44%) in colon cancer tissue sections and preferentially localised either only in the tumour centre or both in the tumour centre and the invasive front. Of note, citrullinated NETs were significantly associated with high histopathological tumour grades and lymph node metastasis.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , purified NETs induced filopodia formation and cell motility in CRC cell lines. This was associated with increased expression of mesenchymal marker mRNAs (vimentin [\n                    <jats:italic>VIM<\/jats:italic>\n                    ], fibronectin [\n                    <jats:italic>FN1<\/jats:italic>\n                    ]) and epithelial\u2013mesenchymal transition promoting transcription factors (\n                    <jats:italic>ZEB1,<\/jats:italic>\n                    Slug [\n                    <jats:italic>SNAI2<\/jats:italic>\n                    ]), as well as decreased expression of the epithelial markers E\u2010cadherin (\n                    <jats:italic>CDH1<\/jats:italic>\n                    ) and epithelial cell adhesion molecule (\n                    <jats:italic>EPCAM<\/jats:italic>\n                    ). These findings indicated that NETs activate an epithelial\u2013mesenchymal transition\u2010like process in CRC cells and may contribute to the metastatic progression of CRC. \u00a9 2021 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5860","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T17:26:26Z","timestamp":1640280386000},"page":"455-467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["Neutrophil extracellular traps drive epithelial\u2013mesenchymal transition of human colon cancer"],"prefix":"10.1002","volume":"256","author":[{"given":"Antonia M","family":"Stehr","sequence":"first","affiliation":[{"name":"Division of Molecular and Experimental Surgery, Translational Research Center, Department of Surgery Friedrich\u2010Alexander University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Molecular and Experimental Surgery, Translational Research Center, Department of Surgery Friedrich\u2010Alexander University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Demmler","sequence":"additional","affiliation":[{"name":"Division of Molecular and Experimental Surgery, Translational Research Center, Department of Surgery Friedrich\u2010Alexander University (FAU) Erlangen\u2010N\u00fcrnberg and Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc 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