P-selectin (SELP) (SELP)

P-selectin (SELP) is a 140 kDa transmembrane glycoprotein stored in the alpha-granules of platelets and Weibel-Palade bodies of endothelial cells [UniProt: P16109]. Upon stimulation by inflammatory mediators or thrombin, it is rapidly translocated to the cell surface to mediate the initial step of leukocyte recruitment and platelet-vessel wall interactions [PMID: 29330158]. In malignancy, P-selectin plays a critical role by facilitating the binding of platelets to circulating tumor cells (CTCs) via ligands like PSGL-1 or sialyl-Lewis X/A [PMID: 31554631]. This interaction forms a protective microenvironment around tumor cells, shielding them from natural killer (NK) cell-mediated lysis and promoting their adhesion to the endothelium for metastatic seeding [PMID: 28652343]. Therapeutic agents targeting P-selectin, such as the monoclonal antibody crizanlizumab, are primarily used to prevent vaso-occlusive crises in sickle cell disease [FDA: Adakveo]. These drugs are also being investigated for their potential to inhibit cancer metastasis and thrombotic complications by disrupting the physical bridge between platelets and tumor cells [PMID: 30104610]. By blocking the lectin domain of P-selectin, these therapies prevent the formation of tumor-platelet aggregates that are essential for efficient hematogenous spread.

Other names

CD62PGMP-140PADGEMSelectin PGranule membrane protein 140P-selectin-mediated tumor cell–platelet interactions

P-selectin inhibitors bind to the extracellular lectin domain of P-selectin, preventing its interaction with P-selectin glycoprotein ligand-1 (PSGL-1) and other carbohydrate ligands on leukocytes, platelets, and tumor cells [PMID: 30104610].