The roles of P -selectin in cancer cachexia

P -selectin, a cell adhesion molecule of the selectin family, is expressed on the surface of activated endothelial cells (ECs) and platelets. Binding of P -selectin to P -selectin glycoprotein ligand-1 (PSGL-1) supports the leukocytes capture and rolling on stimulated ECs and increases the aggregation of leukocytes and activated platelets. Cancer cachexia is a systemic inflammation disorder characterized by metabolic disturbances, reduced body weight, loss of appetite, fat depletion, and progressive muscle atrophy. Cachexia status is associated with increased pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), which activates ECs to release P -selectin. Single-nucleotide polymorphisms (SNPs) loci of P -selectin encoding gene SELP are associated with higher level of plasma P -selectin and increase the susceptibility to cachexia in cancer patients. Elevated P -selectin expression has been observed in the hypothalamus, liver, and gastrocnemius muscle in animal models with cancer cachexia. Increased P -selectin may cause excessive inflammatory processes, muscle atrophy, and blood hypercoagulation, thus facilitating the development of cancer cachexia. In this review, physiological functions of P -selectin and its potential roles in cancer cachexia have been summarized. We also discuss the therapeutic potential of P -selectin inhibitors for the treatment of cancer cachexia.