Platelets and angiogenesis in malignancy.
Platelets and angiogenesis in malignancy.
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DOI：
10.1055/s-2004-822974
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发表时间：
2004-02
影响因子：
5.7
通讯作者：
E. Sierko;M. Wojtukiewicz
中科院分区：
文献类型：
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作者：
E. Sierko;M. Wojtukiewicz
越来越多的证据表明，血小板在肿瘤血管生成过程中发挥着重要作用。血小板增多症是癌症患者中常见的发现（10-57%）。尽管血小板增多的机制尚未完全阐明，但假定具有促血小板生成素样活性的肿瘤衍生因子和生长因子、血小板衍生微粒和骨髓内皮细胞分泌的因子以及巨核细胞释放的生长因子（通过自分泌环起作用）影响这一过程。癌症的进展与高凝状态有关，高凝状态是由肿瘤细胞的直接影响和多种间接机制引起的。活化的血小板作为促凝血表面放大凝血反应。众所周知，止血蛋白参与血管生成过程的不同步骤。此外，粘附于内皮的血小板促进单核细胞（其发挥各种促血管生成活性）与内皮细胞的粘附以及它们向血管外空间的迁移。还有证据表明血小板可以诱导体内血管生成。血小板是促血管生成因子的丰富来源。它们还储存和释放血管生成抑制剂。此外，血小板表达表面生长因子受体，其可调节血管生成过程。血小板还通过释放蛋白酶直接参与基底膜和细胞外基质的蛋白水解过程，或通过诱导内皮细胞和肿瘤细胞释放蛋白水解酶间接参与基底膜和细胞外基质的蛋白水解过程，以及通过血小板衍生生长因子的蛋白水解活性间接参与基底膜和细胞外基质的蛋白水解过程。血小板在肿瘤发展和转移形成过程中新血管形成过程中的多向活动可能为引入抗血小板药物用于癌症患者的抗血管生成治疗创造了可能性。到目前为止，采用糖蛋白IIb-IIIa抑制剂的实验研究已经取得了有希望的结果。
There is increasing evidence that platelets play an important role in the process of tumor angiogenesis. Thrombocytosis is a frequent finding in cancer patients (10-57%). Although the mechanisms underlying thrombocytosis are not yet fully elucidated, tumor-derived factors with thrombopoietin-like activity and growth factors, platelet-derived microparticles, and factors secreted from bone marrow endothelial cells, as well as growth factors released by megakaryocytes (acting via an autocrine loop), are postulated to influence this process. The progression of cancer is associated with hypercoagulability, which results from direct influences of tumor cells and diverse indirect mechanisms. Activated platelets serve as procoagulant surfaces amplifying the coagulation reactions. It is well known that hemostatic proteins are involved in different steps of the angiogenic process. Furthermore, platelets adhering to endothelium facilitate adhesion of mononuclear cells (which exert various proangiogenic activities) to endothelial cells and their transmigration to the extravascular space. It was also documented that platelets induce angiogenesis in vivo. Platelets are a rich source of proangiogenic factors. They also store and release angiogenesis inhibitors. In addition, platelets express surface growth factor receptors, which may regulate the process of angiogenesis. Platelets also contribute directly to the process of basement membrane and extracellular matrix proteolysis by releasing proteinases, or indirectly via inducing endothelial cells and tumor cells to release proteolytic enzymes, as well as through the proteolytic activities of platelet-derived growth factors. The multidirectional activities of platelets in the process of new blood vessel formation during tumor development and metastasis formation may create the possibility of introducing antiplatelet agents for antiangiogenic therapy in cancer patients. Thus far experimental studies employing inhibitors of glycoprotein IIb-IIIa have yielded promising results.