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Sökning: onr:"swepub:oai:lup.lub.lu.se:fb412bec-e256-402e-a806-3f764ad152ab" > Neutrophil extracel...

Neutrophil extracellular traps promote peritoneal metastasis of colon cancer cells

Al-Haidari, Amr A., (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
Algethami, Nader, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
Lepsenyi, Mattias, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
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Rahman, Milladur, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
Syk, Ingvar, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
Thorlacius, Henrik, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
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2019
Engelska 12 s.
Ingår i: Oncotarget. - Impact Journals, LLC. - 1949-2553. ; 10:12, s. 1238-1249
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Carcinomatosis
Chemokines
Metastases
Neutrophils
Peritoneum

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