Work

Neutrophil serine proteases are internalized by glioblastoma cells and modulate cell mechanics, apoptosis, and migration

Year: 2026

Type: preprint

Abstract: Neutrophil serine proteases (NSPs) are crucial mediators of the immune response, with cathepsin G (CatG) and neutrophil elastase (NE) being prominently released by activated neutrophils during neuroinflammation. Beyond pathogen clearance, NSPs modulate cellular functions through surface binding and internalization. Glioblastoma (GB), the most aggressive primary brain cancer, is characterized by its significant therapeutic resistance and invasive properties. We investigated the effects of CatG and NE on human GB cell lines U87 and A172. Both NSPs were internalized, with NE being mostly sequestered to CD107a+ endocytic compartments. A172 cells were susceptible to NSP-induced apoptosis, whereas U87 cells exhibited resistance. Exposure to CatG or NE significantly reduced cellular stiffness, as revealed by biomechanical profiling via atomic force microscopy (AFM) in U87 and A172 cells, suggesting a protease-mediated transition to a more deformable state. Strikingly, CatG impaired U87 migration, indicating that while softening is often linked to invasion, proteolytic activity may destabilize the structural integrity required for movement. These findings collectively suggest NSP-mediated GB cell plasticity.

Source: Research Square

DOI: 10.21203/rs.3.rs-10752886/v1