UR7516, CHIMERE, Université de Picardie Jules Verne, Amiens, France.
Service de Biochimie, Centre de Biologie Humaine, CHU Amiens, Amiens, France.
Anticancer Res. 2024 Aug;44(8):3269-3276. doi: 10.21873/anticanres.17145.
BACKGROUND/AIM: How tumors regulate the genes of the coagulome is crucial for cancer-associated thrombosis and the occurrence of venous thromboembolic complications in patients with cancer. We have previously reported potent yet complex effects of glucocorticoids (GC) on the expression of three genes that play a key role in the regulation of thrombin/plasmin activation (F3, PLAU, and SERPINE1). This study aimed to extend the investigation of GC effects to the whole tumor coagulome and assess the resulting impact on the ability of cancer cells to activate thrombin and plasmin.
Cancer RNA expression data were retrieved from various sources. Additionally, oral squamous cell carcinoma (OSCC) cells exposed to GC in vitro were analyzed using QPCR, enzymatic assays measuring thrombin and urokinase-type Plasminogen Activator (uPA) activity, and D-dimer concentrations.
Our findings highlight the potent and specific stimulatory effect of GC on SERPINE1 expression across different types of cancer. Consistently, GC were found to inhibit uPA proteolytic activity and reduce the concentrations of D-dimers in OSCC in vitro.
Fibrinolysis inhibition is a key consequence of cancer cell exposure to GC, possibly leading to the stabilization of the fibrin clot in cancer.
背景/目的：肿瘤如何调节凝血组学的基因对于癌症相关血栓形成以及癌症患者发生静脉血栓栓塞并发症至关重要。我们之前报道了糖皮质激素（GC）对三个在凝血酶/纤溶酶激活调节中起关键作用的基因表达的强大但复杂的影响（F3、PLAU 和 SERPINE1）。本研究旨在将 GC 效应的研究扩展到整个肿瘤凝血组学，并评估其对癌细胞激活凝血酶和纤溶酶能力的影响。
从各种来源检索癌症 RNA 表达数据。此外，还使用 QPCR、测量凝血酶和尿激酶型纤溶酶原激活物（uPA）活性以及 D-二聚体浓度的酶测定法，分析了体外暴露于 GC 的口腔鳞状细胞癌（OSCC）细胞。
我们的研究结果强调了 GC 对不同类型癌症中 SERPINE1 表达的强烈和特异性刺激作用。一致地，GC 被发现抑制 uPA 蛋白水解活性并降低体外 OSCC 中的 D-二聚体浓度。
纤溶抑制是癌细胞暴露于 GC 的关键后果，可能导致癌症中纤维蛋白凝块的稳定。
