Neutrophil extracellular traps promote peritoneal metastasis of colon cancer cells

Oncotarget
Amr A Al-HaidariHenrik Thorlacius

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 chemokine-dependent colon cancer cell migration and adhesion in vitro. Finally, CT-26 cancer cells were found to express the αv...Continue Reading

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Citations

Jan 22, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leonardo CristinzianoMaria Rosaria Galdiero
Sep 14, 2019·Circulation Research·Nicoletta SorvilloDenisa D Wagner
Jul 13, 2020·Journal of Thrombosis and Haemostasis : JTH·Charlotte ThålinAndrea L Johnstone
Jul 18, 2020·Annals of Surgery·Jules H EustacheJonathan D Spicer
Oct 20, 2020·Cancer Control : Journal of the Moffitt Cancer Center·Marzena GarleyDorota Dziemiańczyk-Pakieła
Jul 20, 2021·Seminars in Cancer Biology·Leonardo CristinzianoMaria Rosaria Galdiero

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Methods Mentioned

BETA
electron microscopy
fluorescence microscopy
scanning electron microscopy
Transmission electron microscopy
flow cytometry
FACS
density gradient centrifugation
confocal microscopy

Software Mentioned

CytExpert
SigmaPlot

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