Anionic phospholipid-enriched cancer cell membrane

In healthy cells, anionic phospholipids, primarily phosphatidylserine (PS), are actively sequestered to the inner leaflet of the plasma membrane by flippase enzymes (Birge et al., 2016, doi:10.1038/cdd.2016.11). In the tumor microenvironment, factors such as hypoxia, oxidative stress, and acidity cause a loss of this membrane asymmetry, leading to the exposure of PS on the outer leaflet of cancer cells and tumor-associated vascular endothelium (Thorpe, 2010, doi:10.1158/1078-0432.CCR-10-1240). This externalized PS acts as a global immunosuppressive signal, promoting an M2-like macrophage phenotype and inhibiting dendritic cell maturation (He et al., 2019, doi:10.1186/s13045-019-0729-6). Therapeutic agents like bavituximab target these anionic surfaces to reverse immunosuppression and stimulate an anti-tumor immune response (Gerber et al., 2015, doi:10.1158/1078-0432.CCR-14-1311). Additionally, agents like BXQ-350 (SapC-DOPS) exploit the acidic environment and anionic charge to selectively fuse with and destroy cancer cell membranes (Davis et al., 2016, doi:10.1158/1535-7163.MCT-15-0789). This target represents a unique physiological hallmark of cancer that allows for broad-spectrum targeting across various tumor types.

Other names

Phosphatidylserine-exposed membranePS-enriched membraneNegatively charged cancer cell membraneAnionic tumor cell surface

Binding to externalized phosphatidylserine to induce immune-mediated cytotoxicity or direct membrane lysis.