Alteration in platelet function in patients with early breast cancer.

Department of Clinical Biochemistry, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL.
Anticancer research (Impact Factor: 1.71). 01/2005; 25(6B):3963-6.
Source: PubMed

ABSTRACT The aim of this study was to examine our hypothesis that platelets of patients with breast cancer were functionally altered compared to healthy controls. The results have shown that the platelets from women with early breast cancer released significantly more vascular endothelial growth factor (VEGF) when stimulated with thrombin, tissue factor, clotting, or over a period of time. Similarly, release of thrombospondin (TSP) with thrombin and tissue factor was higher, but failed to reach a significant level. Thus, the observed differences in platelet response support our hypothesis, but warrant further work to determine the reason underlying the observed difference and potential clinical relevance of our findings.

0 0
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Abstract Background Venous thromboembolism (VTE) following breast cancer chemotherapy is common. Chemotherapy-induced alterations in markers of haemostasis occur during chemotherapy. In this study we investigated the changes in serum and plasma VEGF, together with platelet release of VEGF and related these to the development of VTE at 3 months. Methods Serum and plasma VEGF, together with platelet release of VEGF were measured prior to chemotherapy and at 24 hours; four-, eight days and three months following commencement of chemotherapy in early and advanced breast cancer patients and in age and sex matched controls. Duplex ultrasound imaging was performed after one month or if symptomatic. Results Of 123 patients 9.8% developed VTE within three months. Serum and plasma VEGF were increased in advanced breast cancer as was platelet release of VEGF. Prior to chemotherapy a 100 μg/ml increase in serum VEGF was associated with a 40% increased risk of VTE, while a 10 μg/ml increase in plasma VEGF was associated with a 20% increased risk of VTE. Serum VEGF showed a different response to chemotherapy in those who developed VTE. Conclusion A group of patients at risk of VTE could be identified, allowing targeted thrombopropylaxis. Whether or not the response in VEGF during chemotherapy has any angiogenic significance remains to be elucidated.
    Journal of Angiogenesis Research 01/2009;
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: To survive and metastasize, tumors interact with surrounding tissues by secreting growth factors and cytokines. In return, surrounding host tissues respond by changing their secretome. Numerous factors theoretically function as therapeutic targets or biomarkers of cancer growth and metastatic risk. However, it is unclear if these factors are tumor-derived or actually represent the host defense. To analyze the concentrations of tumor- and microenvironment-derived factors associated with neoplastic growth, we used ELISA-based arrays specific for murine or human proteins to establish a profile of tumor- or host-derived factors circulating in the plasma or within the platelets upon human tumor implantation into mice. Many factors characterized as tumor-derived were actually secreted by host tissues. This study uncovered the origin of various cytokines and revealed their circulation methods. We found that tumor-produced cytokines are predominantly sequestered in platelets. Sequestered proteins are protected from degradation and, thus, may be functional at metastatic sites. These findings identify tumor-specific targets for the detection and prevention of tumor growth and metastasis. As predicted by our model, monocyte chemotactic protein 1 and tumor necrosis factor alpha may be biomarkers for human cancers. Thus, our study identified several potential biomarkers that might be predictive of prostate cancer.
    Neoplasia (New York, N.Y.) 05/2010; 12(5):388-96. · 5.48 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Angiogenesis alleviates hypoxic stress in ischemic tissues or during tumor progression. In addition to endothelial cell proliferation and migration, the angiogenic process requires bone marrow-derived cell (BMDC) recruitment to sites of neovascularization. However, the mechanism of communication between hypoxic tissues and the BM remains unknown. Using 2 models of hypoxia-induced angiogenesis (ischemic hindlimb surgery and subcutaneous tumor growth), we show that platelet infusion promotes BMDC mobilization into the circulation, BMDC recruitment into growing neovasculature, tumor vascularization, and blood flow restoration in ischemic limbs, whereas platelet depletion inhibits these effects. Thus, platelets are required for BMDC recruitment into ischemia-induced vasculature. Secretion of platelet α-granules, but neither dense granules nor platelet aggregation is crucial for BMDC homing and subsequent angiogenesis, as determined using VAMP-8(-/-), Pearl, and integrin Beta 3(-/-) platelets. Finally, platelets sequester tumor-derived promoters of angiogenesis and BMDC mobilization, which are counterbalanced by the antiangiogenic factor thrombospondin-1. A lack of thrombospondin-1 in platelets leads to an imbalance in proangiogenic and antiangiogenic factors and accelerates tumor growth and vascularization. Our data demonstrate that platelets stimulate BMDC homing in a VAMP-8-dependent manner, revealing a previously unknown role for platelets as key mediators between hypoxic tissues and the bone marrow during angiogenesis.
    Blood 01/2011; 117(14):3893-902. · 9.06 Impact Factor


Available from