Neutrophil extracellular traps promote peritoneal metastasis of colon cancer cells

Research output: Contribution to journalArticle

Abstract

Cytoreductive surgery is the only curative option for patients with peritoneal carcinomatosis, however, intraperitoneal recurrence rate is high making new ways to prevent cancer recurrence an urgent need. Recent evidence suggests that neutrophils are involved in cancer progression. The purpose of our study was to examine the role of neutrophils in the spread of colon cancer cells in the peritoneal cavity. The number of metastatic noduli in the peritoneal cavity was quantified in mice injected with murine colon cancer cells (CT-26) intraperitoneally after surgical laparotomy and treated with a neutrophil depleting antibody or DNase I. In addition, peritoneal metastases were harvested from patients with peritoneal carcinomatosis. Scanning and transmission electron microscopy showed extensive neutrophil extracellular trap (NET) formation in peritoneal colon cancer metastases in mice and patients. Neutrophil depletion markedly reduced the number of metastases in laparotomised animals. Administration of DNase I decreased the number of metastatic nodules by 88% in laparotomised animals as well as NET-induced chemokinedependent colon cancer cell migration and adhesion in vitro. Finally, CT-26 cancer cells were found to express the avβ3 integrin and inhibition of av integrin abolished NET-induced adhesion of colon cancer cells to vitronectin. Taken together, our data show that NETs play an important role in colon cancer cell metastasis in the peritoneal cavity and regulate colon cancer cell migration and adhesion to extracellular matrix proteins. These novel findings suggest that targeting NETs might be an effective strategy to antagonize intrabdominal recurrences of colon cancer after cytoreductive surgery in patients with peritoneal carcinomatosis.

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Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • Carcinomatosis, Chemokines, Metastases, Neutrophils, Peritoneum
Original languageEnglish
Pages (from-to)1238-1249
Number of pages12
JournalOncotarget
Volume10
Issue number12
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes