Evidence and impact of neutrophil extracellular traps in malignant melanoma

• Published in: Pigment cell and melanoma research Vol. 33; no. 1; pp. 63 - 73
• Main Authors: Schedel, Fiona, Mayer‐Hain, Sarah, Pappelbaum, Karin Ingrid, Metze, Dieter, Stock, Martin, Goerge, Tobias, Loser, Karin, Sunderkötter, Cord, Luger, Thomas Anton, Weishaupt, Carsten
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.01.2020
• Subjects: Cell adhesion & migration; Chromatin; Cytotoxicity; Leukocyte migration; Leukocytes (neutrophilic); Melanoma; Necrosis; neutrophil extracellular trap; neutrophil granulocyte; Neutrophils; Skin cancer; Survival; tumor progression; Tumors; ulceration; melanoma; ulceration; neutrophil granulocyte; tumor progression; neutrophil extracellular trap
• ISSN: 1755-1471; 1755-148X; 1755-148X
• DOI: 10.1111/pcmr.12818

Ulceration of melanoma is associated with neutrophil infiltrates and lower survival rates opposite to non‐ulcerated melanoma. Neutrophils release neutrophil extracellular traps (NETs) that are chromatin structures loaded with antimicrobial proteins. Since NETs have been correlated with tumor progression, we investigated whether NETs appear in melanoma and affect melanoma cells. Indeed, human primary melanoma biopsies revealed neutrophils releasing NETs in all of 27 ulcerated melanomas, whereas NETs were absent in all of 7 non‐ulcerated melanomas. However, the quantity of intratumoral NETs did not correlate with tumor progression of melanoma. Interestingly, in vitro assays showed that melanoma cells attach to NETs via integrin‐mediated adhesion and that NETs inhibit tumor cell migration. Moreover, co‐culturing of NETs and melanoma cells had a cytotoxic effect on melanoma cells resulting in necrosis. Hence, we discovered in vitro an antineoplastic role of NETs in melanoma.