Verheul H M, Hoekman K, Lupu F, Broxterman H J, van der Valk P, Kakkar A K, Pinedo H M
Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Clin Cancer Res. 2000 Jan;6(1):166-71.
Angiogenesis and activated blood coagulation are involved in tumor growth and metastasis. Although some have suggested that activation of coagulation in tumors is not linked to activation of platelets, no data exist to either support or refute this concept. However, platelet turnover in cancer patients is often increased, and platelets are carriers of angiogenic growth factors. We hypothesized that platelets are involved in tumor-associated angiogenesis. To obtain evidence supporting this hypothesis, we have studied whether the angiogenic and coagulation pathways and platelets are concomitantly activated in cancer patients with soft tissue sarcomas (STSs) using a novel method to detect activated platelets in tumor specimens. Twelve patients with STS were selected on the basis of having intratumoral accumulation of fluid, which was aspirated. These accumulations demonstrated very high concentrations of vascular endothelial growth factor and coagulation factors (including thrombin-antithrombin-complex). Tumor specimens showed dense vascularization with intense vascular endothelial growth factor expression and the presence of activated platelets. Taken together, these results support the concept that angiogenesis, blood coagulation, and platelets are concomitantly activated in STS and support the hypothesis that platelets contribute to tumor-induced angiogenesis.
血管生成和凝血激活参与肿瘤的生长和转移。尽管有人认为肿瘤中的凝血激活与血小板激活无关,但尚无数据支持或反驳这一观点。然而,癌症患者的血小板周转率通常会增加,且血小板是血管生成生长因子的载体。我们推测血小板参与肿瘤相关的血管生成。为了获得支持这一假设的证据,我们使用一种检测肿瘤标本中活化血小板的新方法,研究了血管生成和凝血途径以及血小板在软组织肉瘤(STS)癌症患者中是否同时被激活。根据肿瘤内有液体聚集这一情况,选取了12例STS患者,并抽取了这些积液。这些积液显示出非常高浓度的血管内皮生长因子和凝血因子(包括凝血酶 - 抗凝血酶复合物)。肿瘤标本显示血管密集,血管内皮生长因子表达强烈,且存在活化血小板。综上所述,这些结果支持了在STS中血管生成、凝血和血小板同时被激活的观点,并支持了血小板促进肿瘤诱导血管生成的假设。