Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France.
Laboratoire d'Hématologie, Centre Hospitalo-Universitaire Conception, Marseille, France.
Semin Thromb Hemost. 2019 Sep;45(6):569-575. doi: 10.1055/s-0039-1693475. Epub 2019 Aug 5.
Cancer-related venous thromboembolism (VTE) is frequent and constitutes the second leading cause of death in patients with cancer. High platelet count is one of independent predictive factors of cancer-associated VTE. Besides the implication of platelets in cancer-associated VTE, recent clinical and experimental evidences support that platelets play several roles in the progression of malignancies and inversely, cancer can also influence platelet count and activity. The objective of this report is to review the current literature regarding the role of platelets in cancer through experimental results and population-based studies. Platelets are implicated in cancer progression and metastasis through proangiogenic factors (growth factors and signaling pathways), antiangiogenic factors (angiostatin, endostatin, thrombospondin-1), and matrix metalloproteinases. In addition, platelets are involved in cancer-associated thrombosis and thus tumor cell-induced platelet activation, through anionic phospholipids on their surface, released soluble factors, such as P-selectin, CD40 ligand, platelet factor 4, thrombospondin-1 or beta-thromboglobulin, tumor cell procoagulant proteins (tissue factor, urokinase-type plasminogen activator, plasminogen activator inhibitor type 1), and microparticles. Due to these different mechanisms, platelets may represent a potential therapeutic target. The main current treatments against platelets are: (1) acetylsalicylic acid (aspirin) and nonsteroidal anti-inflammatory drugs, nonselective cyclo-oxygenase (COX)-1 and COX-2 inhibitors, which are associated with decreased cancer incidence and better overall survival and (2) irreversible inhibitor of P2Y12 subtype which decreases cancer incidence. Platelets are key players in tumor growth, metastasis, and cancer-associated thrombosis. This multifaceted role identifies them as a relevant therapeutic target for prevention of cancer occurrence and treatment of cancer.
癌症相关静脉血栓栓塞症（VTE）较为常见，是癌症患者的第二大死亡原因。血小板计数升高是癌症相关 VTE 的独立预测因素之一。除了血小板在癌症相关 VTE 中的作用外，最近的临床和实验证据表明，血小板在恶性肿瘤的进展中发挥多种作用，相反，癌症也可以影响血小板计数和活性。本报告的目的是通过实验结果和基于人群的研究，综述血小板在癌症中的作用的当前文献。血小板通过促血管生成因子（生长因子和信号通路）、抗血管生成因子（血管抑素、内皮抑素、血栓调节蛋白-1）和基质金属蛋白酶参与癌症的进展和转移。此外，血小板参与癌症相关的血栓形成，从而通过其表面的阴离子磷脂、释放的可溶性因子（如 P-选择素、CD40 配体、血小板因子 4、血栓调节蛋白-1 或β-血栓球蛋白）、肿瘤细胞促凝蛋白（组织因子、尿激酶型纤溶酶原激活物、纤溶酶原激活物抑制剂 1）和微粒参与肿瘤细胞诱导的血小板活化。由于这些不同的机制，血小板可能成为一个潜在的治疗靶点。目前针对血小板的主要治疗方法是：（1）乙酰水杨酸（阿司匹林）和非甾体抗炎药，非选择性环氧化酶（COX）-1 和 COX-2 抑制剂，与降低癌症发生率和更好的总生存率相关，以及（2）P2Y12 亚型不可逆抑制剂，可降低癌症发生率。血小板是肿瘤生长、转移和癌症相关血栓形成的关键参与者。这种多方面的作用将其确定为预防癌症发生和治疗癌症的相关治疗靶点。
