1 Department of Stomatology, First Hospital, Harbin Medical University, Harbin, China.
2 Department of Oral Anatomy and Physiology, Stomatology School, Harbin Medical University, Harbin, China.
J Dent Res. 2019 Jul;98(7):763-771. doi: 10.1177/0022034519843106. Epub 2019 Apr 12.
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 ( = 63) as well as healthy controls ( = 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.
磷脂酰丝氨酸（PS）在口腔鳞状细胞癌（OSCC）患者形成高凝状态中的具体作用尚不清楚。因此，本研究旨在评估 PS 在微粒（MPs）以及内皮细胞和血细胞上的暴露情况，并评估促凝活性（PCA）与 OSCC 进展阶段的关系。我们招募了患有 OSCC（n=63）的患者和健康对照者（n=26）参与本研究。然后通过共聚焦显微镜和流式细胞术评估 PS 暴露情况，结果显示，III/IV 期 OSCC 患者的 PS 暴露血细胞、MPs 和血清培养的内皮细胞（ECs）频率高于 I/II 期 OSCC 患者或健康对照者。当我们进行功能凝血测定时，我们发现 III/IV 期 OSCC 患者的 PS 血细胞、MPs 和血清培养的 ECs 介导的凝血更快，产生的 FXa、凝血酶和纤维蛋白更多。当用 PS 拮抗剂乳酰脱氢酶处理样本时，PCA 被破坏了 80%。引人注目的是，当对接受切除术的 III/IV 期 OSCC 患者的术前和术后样本进行比较时，术后样本中的 PCA 显著降低。在用炎症细胞因子刺激 EC 后，我们通过共聚焦显微镜发现它们在细胞膜上暴露 PS，从而产生 FVa 和 FXa 结合位点，并介导纤维蛋白的形成。综上所述，我们的研究结果表明 PS 血细胞和 MPs 是晚期 OSCC 患者形成高凝和血栓前状态的重要介质。因此，PS 阻断可能是治疗此类患者的可行治疗策略。
