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Here, we identified that neutrophil influx into the omentum is a prerequisite premetastatic step in orthotopic ovarian cancer models. Ovarian tumor\u2013derived inflammatory factors stimulated neutrophils to mobilize and extrude chromatin webs called neutrophil extracellular traps (NETs). NETs were detected in the omentum of ovarian tumor\u2013bearing mice before metastasis and of women with early-stage ovarian cancer. NETs, in turn, bound ovarian cancer cells and promoted metastasis. Omental metastasis was decreased in mice with neutrophil-specific deficiency of peptidylarginine deiminase 4 (PAD4), an enzyme that is essential for NET formation. Blockade of NET formation using a PAD4 pharmacologic inhibitor also decreased omental colonization. Our findings implicate NET formation in rendering the premetastatic omental niche conducive for implantation of ovarian cancer cells and raise the possibility that blockade of NET formation prevents omental metastasis.<\/jats:p>","DOI":"10.1084\/jem.20181170","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T15:24:16Z","timestamp":1545233056000},"page":"176-194","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":441,"title":["Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum"],"prefix":"10.1084","volume":"216","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2025-1555","authenticated-orcid":true,"given":"WonJae","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song Yi","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhaned S.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary A.","family":"Kenny","sequence":"additional","affiliation":[{"name":"Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst","family":"Lengyel","sequence":"additional","affiliation":[{"name":"Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1758-7605","authenticated-orcid":true,"given":"Honami","family":"Naora","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,12,19]]},"reference":[{"key":"2023072604580619400_bib1","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jim.2014.05.009","article-title":"Comparative analysis of the efficiency and specificity of myeloid-Cre deleting strains using ROSA-EYFP reporter mice","volume":"408","author":"Abram","year":"2014","journal-title":"J. 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