Tumor regionalization after surgery: Roles of the tumor microenvironment and neutrophil extracellular traps

Abstract

Surgery is unanimously regarded as the primary strategy to cure solid tumors in the early stages but is not always used in advanced cases. However, tumor surgery must be carefully considered because the risk of metastasis could be increased by the surgical procedure. Tumor surgery may result in a deep wound, which induces many biological responses favoring tumor metastasis. In particular, NETosis, which is the process of forming neutrophil extracellular traps (NETs), has received attention as a risk factor for surgery-induced metastasis. To reduce cancer mortality, researchers have made efforts to prevent secondary metastasis after resection of the primary tumor. From this point of view, a better understanding of surgery-induced metastasis might provide new strategies for more effective and safer surgical approaches. In this paper, recent insights into the surgical effects on metastasis will be reviewed. Moreover, in-depth opinions about the effects of NETs on metastasis will be discussed. Cancer treatment: Understanding risk of spread after surgery Therapies that limit the formation of web-like structures formed by white cells known as neutrophils may lower the risk of cancer spread (metastasis) following surgical tumor removal. Removing solid tumors remains a key cancer treatment, but in some cases surgery itself increases the risk of metastasis. Jong-Wan Park at Seoul National University, South Korea, and co-workers reviewed current understanding of metastasis following surgery. Surgical removal destroys the architecture supporting cancer cells but this can release tumor cells into blood vessels. The stress of deep wounds also affects immune responses, most notably neutrophil extracellular traps (NETs), web-like structures formed by neutrophils to trap and kill pathogens. NETs have previously been implicated in metastasis. In a post-surgical environment enriched in neutrophils and pro-inflammatory cytokines, NET formation may help cancer cells thrive, promoting metastasis.