The Interaction of Selectins and PSGL-1 as a Key Component in Thrombus Formation and Cancer Progression

Abstract

Cellular interaction is inevitable in the pathomechanism of human disease. Formation of heterotypic cellular aggregates, between distinct cells of hematopoietic and nonhematopoietic origin, may be involved in events leading to inflammation and the complex process of cancer progression. Among adhesion receptors, the family of selectins with their ligands have been considered as one of the major contributors to cell-cell interactions. Consequently, the inhibition of the interplay between selectins and their ligands may have potential therapeutic benefits. In this review, we focus on the current evidence on the selectins as crucial modulators of inflammatory, thrombotic, and malignant disorders. Knowing that there is promiscuity in selectin binding, we outline the importance of a key protein that serves as a ligand for all selectins. This dimeric mucin, the P-selectin glycoprotein ligand 1 (PSGL-1), has emerged as a major player in inflammation, thrombus, and cancer development. We discuss the interaction of PSGL-1 with various selectins in physiological and pathological processes with particular emphasis on mechanisms that lead to severe disease.

Life and death of circulating cell-free DNA

“…97 Platelets induce NETosis by releasing thromboxane A2; then, in turn, NETosis leads to thrombin generation. 37,98 Lymphocytes, monocytes, and neutrophils can also release mtDNA strands. 93 In the blood, mtDNA can be present in both particle-associated and non-particle associated forms.…”

P-Selectin Glycoprotein Ligand-1 Gene Polymorphisms in Sudanese Pregnant Women With Thrombosis

“…In Sudan, no previous study bound thrombotic pregnant women with PSGL-1 levels or gene polymorphism in patients compared with normal pregnant women that we have done in this study although many studies suggest that there is a strong relationship between PSGL-1 levels and their genetic polymorphisms and thrombosis [18]. A study done by Kappelmayer and Nagy suggests that PSGL-1 and other selectin ligands represent diagnostic biomarkers and ideal targets for the intervention of thrombosis and cancer [22]. Recently, many studies have demonstrated the functional relevance of PSGL-1 polymorphism and different forms of cardiovascular diseases [23], and this indicates that the P-selectin/ PSGL polymorphism may be important in initiating thrombosis in pregnant women and suggests that detection of P-selectin/PSGL polymorphisms in those categories should be made to avoid pregnancy complications.…”

Sialic acid and biology of life: An introduction

“…P-selectin and E-selectin play a vital role in human implantation [349]. PSGL-1 is now known as a major participant in inflammation, thrombus, along with cancer [350]. Due to their role in cancer immune system modulation they are being studied as possible targets for controlling tumor immunity [351].…”