Department of Dermatology, Venereology and Allergology, Georg August University, Göttingen, Germany.
Blood. 2010 Apr 29;115(17):3427-36. doi: 10.1182/blood-2009-10-247296. Epub 2010 Mar 1.
The general notion that functional platelets are important for successful hematogenous tumor metastasis has been inaugurated more than 4 decades ago and has since been corroborated in numerous experimental settings. Thorough preclinical investigations have, at least in part, clarified some specifics regarding the involvement of platelet adhesion receptors, such as thrombin receptors or integrins, in the metastasis cascade. Pivotal preclinical experiments have demonstrated that hematogenous tumor spread was dramatically diminished when platelets were depleted from the circulation or when functions of platelet surface receptors were inhibited pharmacologically or genetically. Such insight has inspired researchers to devise novel antitumoral therapies based on targeting platelet receptors. However, several mechanistic aspects underlying the impact of platelet receptors on tumor metastasis are not fully understood, and agents directed against platelet receptors have not yet found their way into the clinic. In addition, recent results suggesting that targeted inhibition of certain platelet surface receptors may even result in enhanced experimental tumor metastasis have demonstrated vividly that the role of platelets in tumor metastasis is more complex than has been anticipated previously. This review gives a comprehensive overview on the most important platelet receptors and their putative involvement in hematogenous metastasis of malignant tumors.
普遍认为，功能正常的血小板对于成功的血液恶性肿瘤转移至关重要，这一观点早在 40 多年前就已提出，并在众多实验环境中得到了证实。深入的临床前研究至少部分阐明了血小板黏附受体（如凝血酶受体或整合素）在转移级联反应中的一些具体作用。关键的临床前实验表明，当从循环中清除血小板或通过药理学或遗传学抑制血小板表面受体的功能时，血液恶性肿瘤的扩散显著减少。这种见解促使研究人员设计基于靶向血小板受体的新型抗肿瘤疗法。然而，血小板受体对肿瘤转移影响的一些机制方面尚未完全了解，针对血小板受体的药物也尚未进入临床应用。此外，最近的研究结果表明，靶向抑制某些血小板表面受体甚至可能导致实验性肿瘤转移的增强，这生动地表明，血小板在肿瘤转移中的作用比以前预期的更为复杂。本文综述了最重要的血小板受体及其在恶性肿瘤血液转移中的潜在作用。
