Fig. 2

NETs promote metastasis both on primary tumor and at distant sites. NETs can induce the Epithelial-Mesenchymal Transition (EMT) of primary tumor cells, which arms the cancer cells with motility and invasiveness. The cancer cells invading into the circulation are termed as circulating tumor cells (CTCs), which are shielded and protected by NETs from the attack of various immune cells and fluid shear forces. NETs can also modulate the pre-metastatic niche, including the establishment of an inflammatory and immune evasion milieu, the enhancement of Angiogenesis and vascular permeability. In addition, NETs can drive the dormant cancer cells re-entering the cell cycle and thus reinitiation of aggressive metastatic outgrowth