CTC-neutrophil interaction: A key driver and therapeutic target of cancer metastasis
Chengyi Hu, Ling Long, Jie Lou, Mingjing Leng, Qingqing Yang, Xiang Xu, Xing Zhou
Abstract
Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and enter the bloodstream, where they can seed new metastatic lesions in distant organs. CTCs are often associated with white blood cells (WBCs), especially neutrophils, the most abundant and versatile immune cells in the blood. Neutrophils can interact with CTCs through various mechanisms, such as cell-cell adhesion, cytokine secretion, protease release, and neutrophil extracellular traps (NETs) formation. These interactions can promote the survival, proliferation, invasion, and extravasation of CTCs, as well as modulate the pre-metastatic niche and the tumor microenvironment. Therefore, inhibiting CTC-neutrophils interaction could be a potential strategy to reduce tumor metastasis and improve the prognosis of cancer patients. In this review, we summarize the current literature on CTC-neutrophils interaction’ role in tumor metastasis and discuss the possible therapeutic approaches to target this interaction. • CTC-neutrophil interaction aids metastasis by facilitating invasion, protecting from stress, and modulating microenvironment. • Neutrophils interact with CTCs via adhesion, cytokine secretion, protease release, and NETs formation. • CTC-neutrophil clusters form through adhesion molecules, chemokines, cytokines, ligands, selectins, or NETs. • Targeting neutrophils or CTC-neutrophil interactions may represent a promising strategy to inhibit cancer metastasis.