Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Levels of activated platelet-derived microvesicles in patients with soft tissue sarcoma correlate with an increased risk of venous thromboembolism

Authors: A. Fricke, P. V. Ullrich, A. F. V. Cimniak, C. Becherer, M. Follo, J. Heinz, J. Scholber, G. W. Herget, O. Hauschild, U. A. Wittel, G. B. Stark, H. Bannasch, D. Braig, S. U. Eisenhardt

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

Microvesicles are small vesicles expressing specific antigens from their cells of origin. Elevated levels of microvesicles have been shown to be associated with coagulation disorders as well as with different types of malignancies. This study aims to evaluate a possible correlation of different microvesicle subpopulations with a positive history of venous thromboembolism (VTE) in patients with soft tissue sarcoma.

Methods

Annexin V - positive microvesicles, leukocyte (CD45-positive), platelet (CD61-positive), activated platelet (CD62P-, CD63-positive), endothelium-derived (CD62E-positive) and tissue-factor (CD142-positive) microvesicles were identified in the peripheral blood of patients with soft tissue sarcoma (n = 39) and healthy controls (n = 17) using fluorescence-activated cell sorting (FACS).

Results

Both the total amount of Annexin V-positive microvesicles and levels of endothelium-derived (CD62E-positive) microvesicles were shown to decrease significantly after tumor resection (n = 18, p = 0.0395 and p = 0.0109, respectively). Furthermore, the total amount of Annexin V – positive microvesicles as well as leukocyte (CD45-positive) and endothelium-derived (CD62E-positive) microvesicles were significantly higher in patients with grade 3 (G3) soft tissue sarcoma (n = 9) compared to healthy controls (n = 17) (p = 0.0304, p = 0.0254 and p = 0.0357, respectively). Moreover, patients with G3 soft tissue sarcoma (n = 9) presented higher levels of Annexin V-positive and endothelium-derived (CD62E-positive) microvesicles compared to patients with grade 2 (G2) soft tissue sarcoma (n = 8) (p = 0.0483 and p = 0.0045). Patients with grade 1 (G1) soft tissue sarcoma (n = 3) presented with significantly lower levels of platelet (CD61-positive) microvesicles than patients with G3 soft tissue sarcoma (n = 9) (p = 0.0150).
In patients with a positive history of VTE (n = 11), significantly higher levels of activated platelet (CD62P- and CD63-positive) microvesicles (p = 0.0078 and p = 0.0450, respectively) were found compared to patients without a history of VTE (n = 28).

Conclusion

We found significantly higher levels of Annexin V-positive and endothelium-derived (CD62E-positive) microvesicles to be circulating in the peripheral blood of patients with G3 soft tissue sarcoma compared to patients with G2 soft tissue sarcoma. Furthermore, we showed that high counts of activated platelet-derived microvesicles correlate with the occurrence of VTE. Thus, the detection of these microvesicles might be an interesting new tool for early diagnosis of soft tissue sarcoma patients with increased risk for VTE, possibly facilitating VTE prevention by earlier use of thromboprophylaxis.
Appendix
Available only for authorised users
Literature
1.
Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res. 2010;107:1047–57.CrossRefPubMed
2.
Horstman LL, Ahn YS. Platelet microparticles: a wide-angle perspective. Onc Hem. 1999;30:111–42.
3.
Burnier L, Fontana P, Kwak BR, Angelillo-Scherrer A. Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost. 2009;101:439–51.PubMed
4.
Nomura S, Ozaki Y, Ikeda Y. Function and role of microparticles in various clinical settings. Thromb Res. 2008;123:8–23.CrossRefPubMed
5.
Bakouboula B, Morel O, Faure A, Zobairi F, Jesel L, Trinh A, et al. Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008;177:536–43.CrossRefPubMed
6.
Lynch SF, Ludlam CA. Plasma microparticles and vascular disorders. Br J Haematol. 2007;137:36–48.PubMed
7.
van der Zee PM, Biro E, Ko Y, de Winter RJ, Hack CE, Sturk A, et al. P-selectin- and CD63-exposing platelet microparticles reflect platelet activation in peripheral arterial disease and myocardial infarction. Clin Chem. 2006;52:657–64.CrossRefPubMed
8.
Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One. 2008;3:e3694.CrossRefPubMedPubMedCentral
9.
Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, et al. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer. 2005;113:752–60.CrossRefPubMed
10.
Kim HK, Song KS, Park YS, Kang YH, Lee YJ, Lee KR, 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;39:184–91.CrossRefPubMed
11.
Setzer F, Oberle V, Blass M, Moller E, Russwurm S, Deigner HP, et al. Platelet-derived microvesicles induce differential gene expression in monocytic cells: a DNA microarray study. Platelets. 2006;17:571–6.CrossRefPubMed
12.
Majka M, Kijowski J, Lesko E, Gozdizk J, Zupanska B, Ratajczak MZ. Evidence that platelet-derived microvesicles may transfer platelet-specific immunoreactive antigens to the surface of endothelial cells and CD34+ hematopoietic stem/ progenitor cells--implication for the pathogenesis of immune thrombocytopenias. Folia Histochem Cytobiol. 2007;45:27–32.PubMed
13.
Del Conde I, Shrimpton CN, Thiagarajan P, Lopez JA. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood. 2005;106:1604–11.CrossRefPubMed
14.
Barry OP, Pratico D, Lawson JA, FitzGerald GA. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. J Clin Invest. 1997;99:2118–27.CrossRefPubMedPubMedCentral
15.
Toth B, Liebhardt S, Steinig K, Ditsch N, Rank A, Bauerfeind I, et al. Platelet-derived microparticles and coagulation activation in breast cancer patients. Thromb Haemost. 2008;100:663–9.PubMed
16.
Osterud B. The role of platelets in decrypting monocyte tissue factor. Semin Hematol. 2001;38:2–5.CrossRefPubMed
17.
Davila M, Amirkhosravi A, Coll E, Desai H, Robles L, Colon J, et al. Tissue factor-bearing microparticles derived from tumor cells: impact on coagulation activation. J Thromb Haemost. 2008;6:1517–24.CrossRefPubMed
18.
Zwicker JI, Liebman HA, Neuberg D, Lacroix R, Bauer KA, Furie BC, et al. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res. 2009;15:6830–40.CrossRefPubMedPubMedCentral
19.
Blom JW, Vanderschoot JP, Oostindier MJ, Osanto S, van der Meer FJ, Rosendaal FR. Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost. 2006;4:529–35.CrossRefPubMed
20.
Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006;166:458–64.CrossRefPubMed
21.
22.
Paz-Priel I, Long L, Helman LJ, Mackall CL, Wayne AS. Thromboembolic events in children and young adults with pediatric sarcoma. J Clin Oncol. 2007;25:1519–24.CrossRefPubMed
23.
Jayachandran M, Miller VM, Heit JA, Owen WG. Methodology for isolation, identification and characterization of microvesicles in peripheral blood. J Immunol Methods. 2012;375:207–14.CrossRefPubMed
24.
Toth B, Nieuwland R, Liebhardt S, Ditsch N, Steinig K, Stieber P, et al. Circulating microparticles in breast cancer patients: a comparative analysis with established biomarkers. Anticancer Res. 2008;28:1107–12.PubMed
25.
Laresche C, Pelletier F, Garnache-Ottou F, Lihoreau T, Biichle S, Mourey G, et al. Increased levels of circulating microparticles are associated with increased procoagulant activity in patients with cutaneous malignant melanoma. J Invest Dermatol. 2014;134:176–82.CrossRefPubMed
26.
Liebhardt S, Ditsch N, Nieuwland R, Rank A, Jeschke U, Von Koch F, et al. CEA-, Her2/neu-, BCRP- and Hsp27-positive microparticles in breast cancer patients. Anticancer Res. 2010;30:1707–12.PubMed
27.
Laresche C, Pelletier F, Garnache-Ottou F, Lihoreau T, Biichle S, Mourey G, et al. Increased levels of circulating microparticles are associated with increased procoagulant activity in patients with cutaneous malignant melanoma. J Invest Dermatol. 2013;134:176–82.CrossRefPubMed
28.
Villmow T, Kemkes-Matthes B, Matzdorff AC. Markers of platelet activation and platelet-leukocyte interaction in patients with myeloproliferative syndromes. Thromb Res. 2002;108:139–45.CrossRefPubMed
29.
Blann AD, Gurney D, Wadley M, Bareford D, Stonelake P, Lip GY. Increased soluble P-selectin in patients with haematological and breast cancer: a comparison with fibrinogen, plasminogen activator inhibitor and von Willebrand factor. Blood Coagul Fibrinolysis. 2001;12:43–50.CrossRefPubMed
30.
Hron G, Kollars M, Weber H, Sagaster V, Quehenberger P, Eichinger S, et al. Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost. 2007;97:119–23.PubMed
31.
Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation. 2003;107:I17–21.PubMed
32.
Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003;349:146–53.CrossRefPubMed
33.
Khorana AA, Francis CW, Kuderer NM, Carrier M, Ortel TL, Wun T, et al. Dalteparin thromboprophylaxis in cancer patients at high risk for venous thromboembolism: a randomized trial. Thromb Res. 2017;epub ahead of print.
34.
Donnellan E, Khorana AA. Cancer and venous thromboembolic disease: a review. Oncologist. 2017;epub ahead of print.
Metadata
Title
Levels of activated platelet-derived microvesicles in patients with soft tissue sarcoma correlate with an increased risk of venous thromboembolism
Authors
A. Fricke
P. V. Ullrich
A. F. V. Cimniak
C. Becherer
M. Follo
J. Heinz
J. Scholber
G. W. Herget
O. Hauschild
U. A. Wittel
G. B. Stark
H. Bannasch
D. Braig
S. U. Eisenhardt
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3515-y

Other articles of this Issue 1/2017

BMC Cancer 1/2017 Go to the issue

Research article

A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma

Research article

A novel FOXO1-mediated dedifferentiation blocking role for DKK3 in adrenocortical carcinogenesis

Research article

Therapeutic potential of TAS-115 via c-MET and PDGFRα signal inhibition for synovial sarcoma

Study protocol

Study protocol of the TIRED study: a randomised controlled trial comparing either graded exercise therapy for severe fatigue or cognitive behaviour therapy with usual care in patients with incurable cancer

Study protocol

The ANDROMEDA prospective cohort study: predictive value of combined criteria to tailor breast cancer screening and new opportunities from circulating markers: study protocol

Research article

A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits