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Thromb Haemost 2013; 110(02): 378-385
DOI: 10.1160/TH12-12-0957
Cellular Proteolysis and Oncology
Schattauer GmbH

Circulating microparticles of glial origin and tissue factor bearing in high-grade glioma: a potential prothrombotic role

Maria Teresa Sartori
1   2nd Chair of Internal Medicine, Department of Cardiologic, Thoracic and Vascular Sciences, University Hospital, Padua, Italy
,
Alessandro Della Puppa
2   Neurosurgery, Department of Neurosciences, University Hospital, Padua, Italy
,
Andrea Ballin
1   2nd Chair of Internal Medicine, Department of Cardiologic, Thoracic and Vascular Sciences, University Hospital, Padua, Italy
,
Elena Campello
1   2nd Chair of Internal Medicine, Department of Cardiologic, Thoracic and Vascular Sciences, University Hospital, Padua, Italy
,
Claudia Maria Radu
1   2nd Chair of Internal Medicine, Department of Cardiologic, Thoracic and Vascular Sciences, University Hospital, Padua, Italy
,
Graziella Saggiorato
1   2nd Chair of Internal Medicine, Department of Cardiologic, Thoracic and Vascular Sciences, University Hospital, Padua, Italy
,
Domenico d’Avella
2   Neurosurgery, Department of Neurosciences, University Hospital, Padua, Italy
,
Renato Scienza
2   Neurosurgery, Department of Neurosciences, University Hospital, Padua, Italy
,
Giuseppe Cella
1   2nd Chair of Internal Medicine, Department of Cardiologic, Thoracic and Vascular Sciences, University Hospital, Padua, Italy
,
Paolo Simioni
1   2nd Chair of Internal Medicine, Department of Cardiologic, Thoracic and Vascular Sciences, University Hospital, Padua, Italy
› Author Affiliations
Further Information

Publication History

Received: 30 December 2012

Accepted after major revision: 09 May 2013

Publication Date:
04 December 2017 (online)

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Summary

Venous thromboembolism (VTE) may complicate the clinical course of glioblastoma multiforme (GBM). Circulating microparticles (MPs) have been associated with cancer-related VTE. Sixty-one consecutive patients with GBM undergoing gross-total (41) or subtotal (20) surgical resection followed by radio-chemotherapy were prospectively evaluated. MPs numbers according to cellular origin and the procoagulant activity of annexin V positive (AV+) MPs (MP-activity) were measured before surgery and then 1 week and 1, 4, and 7 months after surgery. Glial (GFAP+) and endothelial (CD62E+) derived MPs, AV+ and tissue factor-bearing (TF+) MPs were measured using flow cytometry. Baseline levels of GFAP+/TF-, TF+/GFAP-, and GFAP+/TF+ MPs were significantly higher in GBM patients than in healthy controls, and significantly increased at each time point after surgery; at 7 months, a further significant increase over the level found a week after surgery was only seen in the subtotally resected patients. The number AV+/CD62E- MPs increased in GBM patients and correlated with MP activity. TF+/GFAP- MPs numbers were significantly higher in 11 GBM patients who developed VTE than in those who did not (p 0.04). TF+/GFAP- MPs levels above the 90th percentile (calculated in GBM patients without VTE) were associated with a higher risk of VTE (RR 4.17, 95% CI 1.57–11.03). In conclusion, the numbers of glial-derived and/or TF-bearing MPs were high in GBM patients both before and even more after the neoplasm was treated, especially in patients with subtotal resection likely according to disease progression. A contribution of TF+/GFAP- MPs to the risk of VTE is suggested.

Keywords

Glioblastoma multiforme - microparticles - tissue factor - tissue factor bearing microparticles - venous thromboembolism
 

  • References

  • 1 Wun T, White RH. Venous thromboembolism (VTE) in patients with cancer: epidemiology and risk factors. Cancer Invest 2009; 27: 63-74.
    CrossrefPubMedGoogle Scholar
  • 2 Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res 2010; 125: 490-493.
    CrossrefPubMedGoogle Scholar
  • 3 Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol 2005; 06: 401-410.
    CrossrefPubMedGoogle Scholar
  • 4 van den Berg YW, Osanto S, Reitsma PH. et al. The relationship between tissue factor and cancer progression: insights from bench and bedside. Blood 2012; 119: 924-932.
    CrossrefPubMedGoogle Scholar
  • 5 Nomura S, Ozaki Y, Ikeda Y. Function and role of microparticles in various clinical settings. Thromb Res 2008; 123: 8-23.
    CrossrefPubMedGoogle Scholar
  • 6 Morel O, Jesel L, Freyssinet JM. et al. Cellular mechanisms underlying the formation of circulating microparticles. Arterioscler Thromb Vasc Biol 2011; 31: 15-26.
    CrossrefPubMedGoogle Scholar
  • 7 Roos MA, Gennero L, Denysenko T. et al. Microparticles in physiological and pathological conditions. Cell Biochem Funct 2010; 28: 539-548.
    CrossrefPubMedGoogle Scholar
  • 8 Zwicker JI, Trenor 3rd CC, Furie BC. et al. Tissue factor-bearing microparticles and thrombus formation. Arterioscler Thromb Vasc Biol 2011; 31: 728-733.
    CrossrefPubMedGoogle Scholar
  • 9 Owens III AP, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res 2011; 108: 1284-1297.
    CrossrefPubMedGoogle Scholar
  • 10 Campello E, Spiezia L, Radu CM. et al. Endothelial, platelet, and tissue factorbearing microparticles in cancer patients with and without venous thromboembolism. Thromb Res 2011; 127: 473-477.
    CrossrefPubMedGoogle Scholar
  • 11 Tesselaar ME, Romijn FP, Van der Linden IK. et al. Microparticle-associated tissue factor activity: a link between cancer and thrombosis?. J Thromb Heamost 2007; 05: 520-527.
    PubMedGoogle Scholar
  • 12 Hron G, Kollars M, Weber H. et al. Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost 2007; 97: 119-123.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Zwicker JI, Liebman HA, Neuberg D. et al. Tumour-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 2009; 15: 6830-6840.
    CrossrefPubMedGoogle Scholar
  • 14 Manly DA, Wang J, Glover SL. et al. Increased microparticle tissue factor activity in cancer patients with venous thromboembolism. Thromb Res 2010; 125: 511-512.
    CrossrefPubMedGoogle Scholar
  • 15 Thaler J, Ay C, Weinstabl H. et al. Circulating procoagulant microparticles in cancer patients. Ann Hematol 2011; 90: 447-453.
    CrossrefPubMedGoogle Scholar
  • 16 Bucciarelli P, Martinelli I, Artoni A. et al. Circulating microparticles and risk of venous thromboembolism. Thromb Res 2012; 129: 591-597.
    CrossrefPubMedGoogle Scholar
  • 17 Zahra S, Anderson JAM, Stirling D. et al. Microparticles, malignancy and thrombosis. Br J Haematol 2011; 152: 688-700.
    CrossrefPubMedGoogle Scholar
  • 18 Khorana AA, Francis CW, Menzies KE. et al. Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost 2008; 06: 1983-1985.
    CrossrefPubMedGoogle Scholar
  • 19 Marras LC, Geerts WH, Perry JR. The risk of venous thromboembolism is increased throughout the course of malignant glioma. Cancer 2000; 89: 640-646.
    CrossrefPubMedGoogle Scholar
  • 20 Jenkins EO, Schiff D, Mackman N. et al. Venous thromboembolism in malignant gliomas. J Thromb Haemost 2010; 08: 221-227.
    PubMedGoogle Scholar
  • 21 Semrad JT, O’Donnel R, Wun T. et al. Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg 2007; 106: 601-608.
    CrossrefPubMedGoogle Scholar
  • 22 Sartori MT, Della APuppa, Ballin A. et al. Prothrombotic state in glioblastoma multiforme: an evaluation of the procoagulant activity of circulating microparticles. J Neurooncol 2011; 104: 225-231.
    CrossrefPubMedGoogle Scholar
  • 23 Macdonald DR, Cascino TL, Schold SC. et al. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 1990; 08: 1277-1280.
    CrossrefPubMedGoogle Scholar
  • 24 Abaza MS, Shaban F, Narayan RK. et al. Human glioma associated intermediate filament proteins: overexpression, co-localisation and cross-reactivity. Anticancer Res 1998; 18: 1333-1340.
    PubMedGoogle Scholar
  • 25 Robert S, Poncelet P, Lacroix R. et al. Standardisation of platelet-derived microparticle counting using calibrated beads and a Cytomics FC500 routine cytometer: a first step towards multicenter studies?. J Throm Haemost 2008; 07: 190-197.
    PubMedGoogle Scholar
  • 26 Lacroix R, Robert S, Poncelet P. et al. Standardisation of platelet-derived microparticle enumeration by flow cytometry with calibrated beads: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop. J Thromb Haemost 2010; 08: 2571-2574.
    CrossrefPubMedGoogle Scholar
  • 27 Baran J, Baj-Krzyworzeka M, Weglarczyk K. et al. Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol Immunother 2010; 59: 841-850.
    CrossrefPubMedGoogle Scholar
  • 28 van Aalderen MC, Trappenburg MC, van Schilfgaarde M. et al. Procoagulant myeloblast-derived microparticles in AML patients: changes in numbers and thrombin generation potential during chemotherapy. J Thromb Haemost 2011; 09: 223-226.
    CrossrefPubMedGoogle Scholar
  • 29 Jung CS, Foerch C, Schänzer A. et al. Serum GFAP is a diagnostic marker for glioblastoma multiforme. Brain 2007; 130: 3336-3341.
    CrossrefPubMedGoogle Scholar
  • 30 Rong Y, Belozerov VE, Tucker-Burden C. et al. Epidermal growth factor receptor and PTEN modulate tissue factor expression in glioblastoma through JunD/ activator protein 1 transcriptional activity. Cancer Res 2009; 69: 2540-2549.
    CrossrefPubMedGoogle Scholar
  • 31 Milsom CC, Yu JL, Mackman N. et al. Tissue factor regulation by epidermal growth factor receptor and epithelial-to-mesenchymal transitions: effect on tumour initiation and angiogenesis. Cancer Res 2008; 68: 10068-10076.
    CrossrefPubMedGoogle Scholar
  • 32 Shinoda J, Yano H, Yoshimura S. et al. Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. J Neurosurg 2003; 99: 597-603.
    CrossrefPubMedGoogle Scholar
  • 33 Kim HK, Song KS, Park YS. et al. Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. Eur J Cancer 2003; 39: 184-191.
    CrossrefPubMedGoogle Scholar
  • 34 Wang JG, Geddings JE, Aleman MM. et al. Tumour-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer. Blood 2012; 119: 5543-5552.
    CrossrefPubMedGoogle Scholar
  • 35 Thaler J, Ay C, Pabinger I. Venous thromboembolism in cancer patients – Risk scores and recent randomised controlled trials. Thromb Haemost 2012; 108: 1042-1048.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Thaler J, Preusser M, Ay C. et al. Intratumoural tissue factor expression and risk of venous thromboembolism in brain tumour patients. Thromb Res 2013; 131: 162-165.
    CrossrefPubMedGoogle Scholar
  • 37 van Doormaal F, Kleinjan A, Berckmans RJ. et al. Coagulation activation and microparticle-associated coagulant activity in cancer patients. An exploratory prospective study. Thromb Haemost 2012; 108: 160-165.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Skog J, Wurdinger T, van Rijn S. et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008; 10: 1470-1476.
    CrossrefPubMedGoogle Scholar
  • 39 Goldhaber SZ, Dunn K, Gerhard-Herman M. et al. Low rate of venous thromboembolism after craniotomy for brain tumour using multimodality prophylaxis. Chest 2002; 122: 1933-1937.
    CrossrefPubMedGoogle Scholar