Department of Hematology/Oncology, Eberhard Karls-University, Otfried-Mueller-Str. 10, Tuebingen, Germany.
Clin Exp Metastasis. 2010 Mar;27(3):141-9. doi: 10.1007/s10585-010-9311-6. Epub 2010 Feb 25.
Data from animal studies indicate that platelets play a key role in tumor dissemination and metastasis. We therefore hypothesized that metastastic cancer patients may display a specific platelet phenotype. Percentage of activated, p-selectin positive platelets as well as platelet contents (i.e., plasma and platelet count-corrected serum levels of VEGF-A, CXCL12, CXCL4, and thrombospondin-1) were analyzed in 43 patients with newly diagnosed metastatic disease prior to treatment. Tumor patients had increased platelet counts and significantly elevated percentages of activated platelets. Moreover, the platelet content of VEGF-A in cancer patients was significantly increased compared to healthy controls, while thrombospondin-1, CXCL12 and CXCL4 were significantly decreased. Our data contain several unexpected results: firstly, CXCL12 was found in minute quantities in the serum as compared with murine studies. Secondly, CXCL4, which was found by mass spectrometry to be the single massively upregulated intraplatelet chemokine in mice after tumor xenotransplantation, was decreased in tumor patient platelets. While increased contents of VEGF-A have been attributed to platelet scavenger activity, the differential decrease of specific platelet contents may be due to differential secretion or altered megakaryopoiesis in metastatic cancer patients.
动物研究数据表明，血小板在肿瘤扩散和转移中起着关键作用。因此，我们假设转移性癌症患者可能表现出特定的血小板表型。在治疗前，我们分析了 43 名新诊断为转移性疾病的患者的血小板激活率（p-选择素阳性血小板的百分比）以及血小板含量（即，血小板计数和校正后的血清 VEGF-A、CXCL12、CXCL4 和血栓调节蛋白-1 水平）。肿瘤患者的血小板计数增加，活化血小板的百分比显著升高。此外，与健康对照组相比，癌症患者的血小板中 VEGF-A 的含量显著增加，而血栓调节蛋白-1、CXCL12 和 CXCL4 的含量显著降低。我们的数据包含了一些意想不到的结果：首先，与小鼠研究相比，我们在血清中发现 CXCL12 的含量非常低。其次，在肿瘤异种移植后，CXCL4 被质谱法发现是小鼠血小板中单个大量上调的趋化因子，但在肿瘤患者的血小板中却减少了。虽然 VEGF-A 含量的增加归因于血小板的吞噬作用，但特定血小板含量的差异减少可能是由于转移性癌症患者的差异分泌或改变的巨核细胞生成。
