Data Sheet 1_Neutrophil extracellular traps promote lung colonization of triple-negative breast cancer by inducing mesenchymal to epithelial transition.docx

Neutrophil extracellular traps (NETs) in the pulmonary microenvironment are known to play key roles in the metastatic colonization and outgrowth of TNBC. However, the exact role that NETs play in determining the phenotypic plasticity and reactivation of disseminated tumor cells (DTCs) during acute relapse remains unclear.

Here, we utilized an orthotopic, acute recurrent metastasis mouse model by transplanting 4T1 cells into wild-type or NET-deficient (Padi4^-/-) mice, followed by primary tumor resection. Although Padi4 deficiency had no effect on the growth of the primary tumors, it significantly reduced lung metastasis and prolonged survival. 4T1 cells re-established from WT lungs displayed a highly proliferative epithelial phenotype, whereas those from Padi4^-/- mice appeared to maintain a quiescent mesenchymal state.