Neutrophil Extracellular Traps in Cancer Metastasis: From Mechanistic Understanding to Targeted Therapy

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Metastasis is the primary cause of cancer mortality.
• Neutrophil extracellular traps (NETs) are increasingly recognized as key regulators of tumor progression and metastasis.

Purpose of the Study:

• To review the stimuli and signaling pathways governing NET formation.
• To outline the mechanistic roles of NET components in tumor growth and metastatic spread.
• To examine the involvement of NETs in the metastatic cascade and immunosuppressive microenvironment.

Main Methods:

• Literature review of primary stimuli, signaling pathways, and mechanistic roles of NETs in cancer metastasis.
• Focus on environmental and tumor microenvironment-derived factors influencing NET formation.
• Discussion of NET involvement across all stages of the metastatic cascade.

Main Results:

• NET formation is driven by psychological stress, cytokines, and treatment responses.
• NETs facilitate angiogenesis, tumor cell intravasation/extravasation, and circulating tumor cell survival.
• NETs contribute to metastatic colonization, reactivation of dormant cells, and an immunosuppressive tumor microenvironment.

Conclusions:

• NETs play multifaceted roles in promoting cancer metastasis.
• Targeting NETs represents a potential therapeutic avenue for metastatic cancers.