Alteration in Platelet Function in Early Breast Cancer

Department of Clinical Biochemistry, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL.
Anticancer research (Impact Factor: 1.83). 11/2005; 25(6B):3963-6. DOI: 10.1042/cs106010Pa
Source: PubMed


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.

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    • "Prostate Castellano et al. [15] Increased with stage, decreased with treatment RANKL 41.40 Neuroblastoma Granchi et al. [16] Increased with stage, metastasis, and unfavorable pathohistology SDF-1α 2448.00 Breast Potter et al. [18] 2661.00 (RL) Hassan et al. [19] Increased metastasis below RL Increased with metastasis 2717.00 (PT) Multiple Zannettino et al. [20] "
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    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. DOI:10.1593/neo.10166 · 4.25 Impact Factor
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    • "VEGF is pro-angiogenic and it has been shown that VEGF secreted by megakaryocytes may contribute to proliferation of vascular endothelial cells [27]. Our previous study has shown that platelets from breast cancer patients release more VEGF per platelet than normal controls [28] "
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    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 10/2009; 1(1). DOI:10.1186/2040-2384-1-7
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    ABSTRACT: Vascular endothelial growth factor (VEGF), a major angiogenic growth factor, is involved in the pathogenesis of cancer. Plasma VEGF is raised in breast cancer and falls after successful surgery. Less is known about angiopoietins 1 and 2 (Ang-1, Ang-2). All three growth factors act on cells via receptors; Flt-1 for VEGF and Tie-2 for the angiopoietins. Cancer is also marked by abnormalities in platelet activation (marked by soluble P selectin) and inflammation (interleukin-6 [IL6]). We hypothesised altered plasma Ang-1, Ang-2, Flt-1 and Tie-2 in breast cancer that would normalize after 3 and 12 months treatment (i.e., surgery plus chemo/radiotherapy). Baseline venous blood was obtained from 40 women with breast cancer and 30 age-matched women with benign breast disease (BBD) also requiring surgery. Samples were taken again 3 months and 1 year later. Soluble P selectin, IL6, VEGF, Ang-1, Ang-2, Flt-1 and Tie-2 were measured in citrated plasma by ELISA. Women with breast cancer had raised VEGF (7-fold), Ang-1 (50% higher) and Tie-2 (2-fold), but lower Flt-1 (to 26%), compared to the BBD women that broadly correlated with markers of platelet activation and inflammation. A level of Tie-2 or VEGF >95th percentile of the BBD group correctly identified 68% and 52% of the women with breast cancer. After 3 months of treatment, VEGF and Ang-1 normalized (as did IL6 and soluble P selectin) but Tie-2 was significantly lower only after 1 year. There were no significant changes in the women with BBD. Treatment for breast cancer (surgery followed by chemotherapy and/or radiotherapy) is effective in reducing plasma VEGF, Tie-2 and Ang-1. These may be linked pathogenically with coagulation and inflammation.
    Cancer Letters 05/2007; 248(1):131-6. DOI:10.1016/j.canlet.2006.06.011 · 5.62 Impact Factor
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