Circulating endothelial and progenitor cells as biomarkers of angiogenesis in pediatric oncology patients
Authors:
D. Zapletalová 1,2; L. Zdražilová Dubská 3; A. Wágnerová 3; M. Kýr 1; J. Štěrba 1,2
Authors place of work:
Klinika dětské onkologie LF MU a FN Brno
1; Mezinárodní centrum klinického výzkumu FN U sv. Anny (FNUSA-ICRC), Brno
2; Masarykův onkologický ústav, Brno
3
Published in the journal:
Čes-slov Pediat 2018; 73 (7): 439-448.
Category:
Original Papers
Summary
Introduction:
Neovascularization by angiogenesis or vasculogenesis is an integral part of the tumor growth, it is essential for tumor invassivness and for the process of metastasis. With the development of antiangiogenic therapies there is urgent need for reliable biomarkers of angiogenesis, that would have both - prognostic and predictive meaning. Circulating endothelial cells (CEC) and circulating endothelial progenitor cells (EPC) have been proposed as a potential noninvasive biomarker of tumor angiogenesis in several studies.
Objective:
The aim of our work was a detailed analysis of the amount of CEC and EPC in pediatric cancer patients, both in relation to tumor type, extent of the disease, type of the treatment response as well as monitoring the dynamics of these cells during treatment.
Patients and methods:
The analysis of objectives in the first part of the research was performed in 171 children. Cells were determined by flowcytometry. We evaluated activated CEC (aCEC) with immunophenotypic definition CD45-CD146+CD105+, mature CEC (mCEC) CD45-CD146+CD31+ and EPC CD45-/+CD146+CD34+.
Results:
We did not find a significant difference in the initial amount of the monitored cells in correlation with the tumor type. Comparing the values before and during treatment, regardless of the diagnosis, there was a decrease in the amount of aCEC and mCEC. In correlation with the treatment response, there was a statistically significant decrease in aCEC in patients who achieved only disease stabilization or progressed on treatment compared to patients who achieved regression in the tumor volume. The extent of the disease and type of the treatment did not have a significant effect on the amount of each of measured endothelial cells.
Conclusions:
In our study, we did not confirm the significance of EPC and CEC as reliable markers in pediatric cancer patients. In practice, aCEC monitoring could be used to identify patients who may be less responsive to treatment. For the further use of EPC and CEC as biomarkers of angiogenesis, a standardized protocol for flowcytometry analysis is required.
KEY WORDS:
angiogenesis, vasculogenesis, circulating enothelial cells, circulating endothelial progenitor cells, pediatric malignancy, flowcytometry
Zdroje
1. Selt F, Deiß A, Korshunov A, et al. Pediatric targeted therapy: Clinical feasibility of personalized diagnostics in children with relapsed and progressive tumors: Pediatric targeted therapy. Brain Pathol 2016; 26 (4): 506–516.
2. Wang W, Zhang E, Lin C. MicroRNAs in tumor angiogenesis. Life Sci 2015; 136: 28–35.
3. Ronca R, Benkheil M, Mitola S, et al. Tumor angiogenesis revisited: Regulators and clinical implications. Med Res Rev 2017; 37 (6): 1231–1274.
4. Van de Broek I. Circulating endothelial cells as a biomarker for angiogenesis in cancer: where do we stand? Belg J Med Oncol 2010; (4): 10–17.
5. Mehran R, Nilsson M, Khajavi M, et al. Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy. Cancer Res 2014; 74 (10): 2731–2741.
6. Schmidt DE, Manca M, Hoefer IE. Circulating endothelial cells in coronary artery disease and acute coronary syndrome. Trends Cardiovasc Med 2015; 25 (7): 578–587.
7. Camus SM, De Moraes JA, Bonnin P, et al. Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease. Blood 2015; 125 (24): 3805–3814.
8. Laurenzana A, Fibbi G, Margheri F, et al. Endothelial progenitor cells in sprouting angiogenesis: Proteases pave the way. Curr Mol Med 2015; 15 (7): 606–620.
9. Madonna R, De Caterina R. Circulating endothelial progenitor cells: Do they live up to their name? Vascul Pharmacol 2015; 67–69: 2–5.
10. Bertolini F, Shaked Y, Mancuso P, Kerbel RS. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 2006; 6 (11): 835–845.
11. Obeid J, Nguyen T, Walker RG, et al. Circulating endothelial cells in children: role of fitness, activity, and adiposity. Med Sci Sports Exerc 2014; 46 (10): 1974–1980.
12. Danova M, Comolli G, Manzoni M, et al. Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation (review). Mol Clin Oncol 2016; 4 (6): 909–917.
13. Espagnolle N, Guilloton F, Deschaseaux F, et al. CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment. J Cell Mol Med 2014; 18 (1): 104–114.
14. Barteneva NS, Vorobjev IA (Eds). Imaging Flow Cytometry. Vol. 1389. New York, NY: Springer New York, 2016.
15. Medina RJ, Barber CL, Sabatier F, et al. Endothelial progenitors: A consensus statement on nomenclature: Endothelial progenitors nomenclature. Stem Cells Transl Med 2017; 6 (5): 1316–1320.
16. Bertolini F, Mancuso P, Braidotti P, et al. The multiple personality disorder phenotype(s) of circulating endothelial cells in cancer. Biochim Biophys Acta BBA – Rev Cancer 2009; 1796 (1): 27–32.
17. Kyr M, Fedora M, Elbl L, et al. Modeling effect of the septic condition and trauma on C-reactive protein levels in children with sepsis: a retrospective study. Crit Care 2007; 11 (3): R70.
18. Taylor M, Rossler J, Geoerger B, et al. High levels of circulating VEGFR2+ bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies. Clin Cancer Res 2009; 15 (14): 4561–4571.
19. DuBois SG, Stempak D, Wu B, et al. Circulating endothelial cells and circulating endothelial precursor cells in patients with osteosarcoma. Pediatr Blood Cancer 2012; 58 (2): 181–184.
20. Pradhan KR, Mund JA, Johnson C, et al. Polychromatic flow cytometry identifies novel subsets of circulating cells with angiogenic potential in pediatric solid tumors. Cytometry B Clin Cytom 2011; 80B (5): 335–338.
21. Pradhan KR, Mund JA, Claussen HL, et al. A pilot study of circulating endothelial and hematopoietic progenitor cells in children with sarcomas. J Pediatr Hematol Oncol 2015; 37 (6): 443–448.
Štítky
Neonatology Paediatrics General practitioner for children and adolescentsČlánok vyšiel v časopise
Czech-Slovak Pediatrics
2018 Číslo 7
- What Effect Can Be Expected from Limosilactobacillus reuteri in Mucositis and Peri-Implantitis?
- The Importance of Limosilactobacillus reuteri in Administration to Diabetics with Gingivitis
Najčítanejšie v tomto čísle
- Possibilities of antibiotic treatment of acute otitis media
- Tubulointerstitial nephritis as a cause of acute renal insufficiency in children
- Hearing loss and hearing impairment in chidhood
- History and present of cochlear implantations in Czechia