The contribution of neutrophils to the etiology of disorders and their development is not restricted to NET formation, but can involve the uptake of toxic granular enzymes, such as NE by surrounding tissues (36, 37). In the first such report, it was noted that the presence of tumor-infiltrating neutrophils can promote tumor cell growth by a mechanism involving NE (36). In this instance, it was determined that exogenous NE released by degranulation was absorbed by surrounding cancer cells where its enzymatic activity led to the degradation of a key regulatory molecule, IRS1. This led to uncoupling of the PI3K signaling pathway, thereby promoting uncontrolled cell growth (36).