Increased Phosphatidylserine on Blood Cells in Oral Squamous Cell Carcinoma

Abstract

The specific function of phosphatidylserine (PS) in the context of the development of a hypercoagulable state among individuals with oral squamous cell carcinoma (OSCC) is uncertain. The goal of this study was therefore to assess the exposure of PS on microparticles (MPs) as well as on endothelial and blood cells and to assess procoagulant activity (PCA) as a function of the stage of OSCC progression. We recruited patients with OSCC ( n = 63) as well as healthy controls ( n = 26) to participate in this study. PS exposure was then assessed via confocal microscopy and flow cytometry, revealing that patients with stage III/IV OSCC exhibited higher frequencies of PS-exposing blood cells, MPs, and serum-cultured endothelial cells (ECs) than did patients with stage I/II OSCC or healthy controls. When we conducted functional coagulation assays, we discovered that PS+blood cells, MPs, and serum-cultured ECs from patients with stage III/IV OSCC mediated more rapid coagulation and more substantial production of FXa, thrombin, and fibrin as compared with controls. When samples were treated with the PS antagonist lactadherin, this resulted in an 80% disruption of PCA. Strikingly, when pre- and postoperative samples were compared from patients with stage III/IV OSCC undergoing resective surgery, PCA was significantly reduced in the postoperative samples. After stimulating ECs with inflammatory cytokines, we found by confocal microscopy that they expose PS on their cell membranes, thus generating FVa and FXa binding sites and mediating the formation of fibrin. Together our findings provide evidence that PS+blood cells and MPs are important mediators of the development of a hypercoagulable and prothrombotic state among individuals afflicted by advanced-stage OSCC. As such, a PS blockade may be a viable therapeutic strategy for treating such patients.

Phosphatidylserine-Gold Nanoparticles (PS-AuNP) Induce Prostate and Breast Cancer Cell Apoptosis

“…Interestingly, our data also showed no major effects on oral cancer cells following treatment with the PS-AuNP. Liu et al [ 48 ] recently reported increased PS in blood cells, microparticles, and serum-cultured endothelial cells in patients with oral squamous cell carcinoma (OSCC) compared to healthy controls. This could indicate that OSCC may use PS over-expression as an immunosuppressive strategy for tumor progression, especially for stage III/IV cancers.…”

Lipidomic Analysis of Plasma from Healthy Men and Women Shows Phospholipid Class and Molecular Species Differences between Sexes

“…PtdSer has been detected in microparticles in blood that have been implicated in hypercoagulation in diabetic kidney disease (Yu et al, 2018), cancer (Lea et al, 2017; Liu et al, 2019; Zhao et al, 2016), and inflammation (Zhao et al, 2016). Whether PtdSer is also an integral component of lipoproteins in humans is not known.…”

The Central Role of Extracellular Vesicles in the Mechanisms of Thrombosis in COVID-19 Patients With Cancer and Therapeutic Strategies

“…Subsequently, FXa binds to FVa to form the prothrombinase complex, which is catalyzed by the PS-rich lipid membrane surface, leading to a burst of thrombin formation, which is required for rapid and local fibrin mesh formation. PS is involved in the amplification phase by binding two types of protein domains: γ-carboxyglutamate-rich (Gla) domains (prothrombin, FVII, FIX, and FX) and C-type lectin domains (FV and FVIII) ( Gilbert et al, 2015 ; Liu et al, 2019 ). Specifically, the assembly of the tenase (factors VIIIa, IXa) and prothrombinase (factors Va, Xa) complexes drive the coagulation cascade.…”