Platelet-derived VEGF, Flt-1, angiopoietin-1 and P-selectin in breast and prostate cancer: further evidence for a role of platelets in tumour angiogenesis

Platelet-derived VEGF, Flt-1, angiopoietin-1 and P-selectin in breast and prostate cancer: further evidence for a role of platelets in tumour angiogenesis
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DOI:
10.1080/07853890410026098
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发表时间:
2004-01-01
期刊:
影响因子:
4.4
通讯作者:
Blann, AD
Blann, AD
中科院分区:
医学3区
文献类型:
--
作者:
Caine, GJ;Lip, GY;Blann, AD

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背景:癌症是一种复杂的多因素疾病,此类患者通常表现为血管生成异常。最近,血小板被认为在这两个过程中都起着重要作用,这表明抗血小板策略可能对癌症治疗有用。材料和方法:为了进一步研究血小板在血管生成中的作用,我们使用了一种新的血小板裂解物测定法来分析乳腺癌(n = 30)和前列腺癌(n = 30)患者以及年龄和性别匹配的对照组(n = 60)的血小板含量。通过酶联免疫吸附法测定血小板裂解液中血管新生标志物(血管内皮生长因子(VEGF)、血管生成素-1和-2 (Ang-1、-2)及其受体(Flt-1和Tie-2)和血小板活化标志物(p -选择素(P-sel))。结果:乳腺癌患者血小板裂解液中VEGF水平较高(P < 0.0001)。Ang-1 (P = 0.0186)和P-sel (P = 0.0002)。前列腺癌患者血小板裂解液中VEGF升高(P = 0.008),而Ang-1或P-sel无升高。患者和对照组之间Flt-1水平无显著差异,两组患者和对照组血小板裂解液中均未检测到Ang-2和Tie-2。结论:我们已经证明,我们先前开发的血小板裂解物技术可以用于测量血管生成的指标,以及它们各自的受体,并且该方法可以应用于癌症患者。我们的研究还提供了进一步的证据,证明血小板可能影响人类癌症的血管生成异常。血小板可能是抗癌策略中一个有用的靶点。
BACKGROUND: Cancer is a complex multi-factorial disorder that may commonly show abnormal angiogenesis in such patients. Recently, platelets have been postulated to have a major role in both these processes, suggesting that antiplatelet strategies may be useful in cancer treatment.MATERIALS AND METHODS: To further investigate the role of platelets in angiogenesis, we used a novel platelet lysate assay to analyse platelet contents in breast cancer (n = 30) and prostate cancer (n = 30) patients and age- and sex-matched controls (n = 60). Markers of angiogenesis (vascular endothelial growth factor (VEGF), angiopoietin-1 and-2 (Ang-1, -2), and their respective receptors (Flt-1 and Tie-2) plus a marker of platelet activation (P-selectin (P-sel)), were all measured in platelet lysate by enzyme-linked immunsorbent assay.RESULTS: Platelet lysate from breast cancer patients contained higher levels of VEGF (P < 0.0001). Ang-1 (P = 0.0186) and P-sel (P = 0.0002), compared to healthy controls. Platelet lysate from prostate cancer patients had elevated VEGF (P = 0.008) but not Ang-1 or P-sel. There were no significant differences between levels of Flt-1 between patients and controls, and both Ang-2 and Tie-2 were undetectable in both patient groups and control platelet lysate.CONCLUSION: We have shown that our previously developed platelet lysate technique could be used to measure indices of angiogenesis, and their respective receptors, and that this assay can be applied to patients with cancer. Our study also provides further evidence that platelets may influence angiogenic abnormalities in human cancer. The platelet may be a useful target in anti-cancer strategies.