Preview

Proceedings of the National Academy of Sciences of Belarus, Medical series

Advanced search

EXPRESSION OF THE ANGIOGENESIS FACTORS OF SARCOMA IN CHILDREN

Abstract

The formation of a new pathological vasculature (angiogenesis) is critical for the cancer development, can reflect the behavior of tumors and can be considered as an angiogenesis inhibitors target. The objective of the study was to find differences in the mRNA (messenger ribonucleic acid) expression levels of varied angiogenesis markers in malignant and non- malignant pathological foci. Angiogenesis markers VEGFA (including isoforms of 121, 165, 189), VEGFC, VEGFR-1, VEGFR-2, VEGFR-3, HIF-1α, TF, TFPI-1, TFPI-2, uPA, PAI-1 in pediatric specimens were examined using quantitative reverse transcriptase–polymerase chain reaction (qRTPCR). 62 (39 malignant and 23 nonmalignant samples) from pediatric patients with bone and soft tissues pathology were studied. A significantly higher level of isoforms VEGFA121, VEGFA165 as well as the VEGFA165/VEGFA189 ratio ascertained for malignancies. Other markers expression levels were higher in patients without cancer pathology. Both, the TFPI-2 level and the VEGFA165/VEGFA189 ratio identified upward for localized cancer vs. metastatic forms (P <0.05). According to our knowledge, this is the first study of such angiogenesis markers combination. The demonstrated expression of several angiogenesis factors is not the extraordinary prerogative of neoplasms and may be greater in patients without malignancy. The VEGFA165/VEGFA189 ratio together with the TFPI-2 level distinguished localized and metastatic cancer patients and can be used as a tumor prognostic marker.

About the Authors

L. KISIALEU
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus


T. SAVITSKAIA
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus


N. LIPAI
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus


O. ALEINIKOVA
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus


References

1. Достижения детской онкологии и гематологии в Республике Беларусь / О. В. Алейникова [и др.] // Актуальные вопросы детской онкологии и гематологии: материалы VIII междунар. симп. – Минск, 2000. – С. 3–8.

2. Суконко, О. Г. Организационно-методическая помощь, оказываемая государственным учреждением РНПЦ ОМР им. Н. Н. Александрова организациям здравоохранения в Республике Беларусь / О. Г. Суконко, Н. А. Антоненкова // Онкол. журн. – 2011. – № 20. – С. 42–45.

3. Неоперируемый рак щитовидной железы: эффективность диагностики и выживаемость / Ю. Е. Демидчик [и др.] // Онкол. журн. – 2008. – № 8. – С. 9–21.

4. Роль молекулярных часов в патогенезе и терапии злокачественных новообразований / Э. А. Жаврид [и др.] // Мед. панорама. – 2011. – № 7. – С. 19–23.

5. Reportingrecom-mendations for tumormarker prognostic studies (REMARK): explanation and elaboration / D. G. Altman [et al.] // BMC Med. – 2012. – N 10. – Р. 51.

6. Adams, R. H. Molecular regulation of angiogenesis and lymphangiogenesis / R. H. Adams, K. Alitalo // Nature. – 2007. – N 8. – Р. 464–468.

7. A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor- 1receptor monoclonal anti- body, inpatients with advanced solid tumors / F. Atzori [et al.] // Clin. Cancer Res. – 2011. – N 17. – Р. 6304–6312.

8. Determination of microvessel density by quantitative real-time PCR in esophageal cancer: correlation with histologic methods, angiogenic growth factor expression and lymph node metastasis / S. Loges [et al.] // Clin. Cancer Res. – 2007. – N 13. – Р. 76–80.

9. Belting, M. Signaling of the tissue factor coagulation pathway in angiogenesis and cancer / M. Belting, J. Ahamed, W. Ruf // Arterioscler. Thromb Vasc. Biol. – 2005. – N 25. – Р. 1545–1550.

10. Ono, M. Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy / M. Ono // Cancer Sci. – 2008. – N 99. – Р. 1501–1506.

11. McMahon, B. The plasminogen activator system and cancer / B. McMahon, H. C. Kwaan // Pathophysiol. Haemost. Thromb. – 2007. – N 8. – Р. 184–194.

12. Wojtukiewicz, M. Z. The role of hemostatic system inhibitors in malignancy / M. Z. Wojtukiewicz, E. Sierko, W. Kisiel // Semin. Thromb Hemost. – 2007. – N 33. – Р. 621–642.

13. VEGF-A splice variants and related receptor expression in human skeletalmuscle following submaximal exercise / T. Gustafsson [et al.] // J. Appl. Physiol. – 2005. – N 98. – Р. 2137–2146.

14. Lu, H. Inflammation, a key event in cancer development / H. Lu, W. Ouyang, C. Huang // Mol. Cancer Res. – 2006. – N 4. – Р. 221–233.

15. Pugh, C. W. Regulation of angiogenesis by hypoxia: role of the HIF system / C. W. Pugh, P. J. Ratcliffe // Nat. Med. – 2003. – N 9. – Р. 677–684.

16. Production of VEGF165 by Ewing’s sarcoma cells induces vasculogenesis and the incorporation of CD34 þ stem cells into the expanding tumor vasculature / T. H. Lee [et al.] // Int. J. Cancer. – 2006. – N 119. – Р. 839–846.

17. DuBois, S. Angiogenesis and Vascular Targeting in Ewing Sarcoma / S. DuBois, N. Marina, J. Glade-Bender // Cancer. – 2010. – N 1. – Р. 749–757.

18. Ferrara, N. The biology of VEGF and its receptors / N. Ferrara, H. P. Gerber, J. Le Couter // Nat. Med. – 2003. – N 9. – Р. 669–676.

19. VEGF121 promotes lymphangiogenesis in the sentinel lymph nodes of non-small cell lung carcinoma patients / H. Kawai [et al.] // Lung Cancer. – 2008. – N 59. – Р. 41–47.


Review

For citations:


KISIALEU L., SAVITSKAIA T., LIPAI N., ALEINIKOVA O. EXPRESSION OF THE ANGIOGENESIS FACTORS OF SARCOMA IN CHILDREN. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2016;(3):99-106. (In Russ.)

Views: 438


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1814-6023 (Print)
ISSN 2524-2350 (Online)