Biopolym. Cell. 2010; 26(3):187-193.
http://dx.doi.org/10.7124/bc.000155
Structure and Function of Biopolymers
Influence of pro-angiogenic cytokines on proliferative activity and survival of endothelial cells
1Garmanchouk L. V., 1Pyaskovskaya O. N., 2Solyanik G. I.
  1. Taras Shevchenko National University of Kyiv
    64, Volodymyrska Str., Kyiv, Ukraine, 01601
  2. R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
    45, Vasilkivska Str., Kyiv, Ukraine, 01022

Abstract

Tumor angiogenesis in contrast to physiological one is characterized by high level of malignant cell production of proangiogenic cytokines, which have different influence on functional activity of endothelial cells. The aim of the study – to carry out a comparative analysis of the influence of a vascular endothelial growth factor (VEGF) and an epidermal growth factor (EGF) on proliferative activity and survival of endothelial cells upon their confluent and exponential growth. Methods. The proliferative activity of endothelial cells was determined by MTT-test and their viability was detected by the trypane blue exclusion test. Results. It was shown that EGF (irrespectively of the level of serum factors) in concentrations higher than 10 ng/ml activated the proliferative activity of confluent endotheliocytes in a concentration-dependent manner by 18–36 % (p < 0.05) as compared to the control, while this cytokine did not affect the endothelial cells in the exponential growth phase. VEGF in wide concentration range did not display the mitogenic effect on endotheliocytes in both confluent and exponential growth phases. Furthermore, VEGF in concentrations higher than 100 ng/ml inhibited proliferative activity of confluent endothelial cells by 12 % (p < 0.05). In case of deficiency of nutrients, EGF and VEGF promoted the survival of endothelial cells, considerably decreasing their death. Conclusions. EGF, in contrast to VEGF, stimulates proliferation and survival of the endothelial cells, whereas VEGF has significant influence only on the survival of the cells.
Keywords: epidermal growth factor (EGF), vascular endothelial growth factor, proliferative activity, endothelial cells
Full text: (PDF, in English) (PDF, in Ukrainian)

References

[1] Risau W. Differentiation of endothelium FASEB J. 1995; 9, N 10:926–933.
[2] Pauly R. R., Passaniti A., Crow M., Kinsella J. L., Papadopoulos N. Monticone R., Lakatta E. G., Martin G. R. Experimental models that mimic the differentiation and dedifferentiation of vascular cells Circullation 1992 86, N 6:III. 68–III.73.
[3] Folkman J., D'amore P. A. Blood vessel formation: What is its molecular basis? Cell 1996 87, N 7:1153–1155.
[4] Joyce N. C., Zhu C. C. Human corneal endothelial cell proliferation: potential for use in regenerative medicine Cornea 2004 23, N 8, Suppl:S8–S19.
[5] Terramani T. T., Eton D., Bui P. A., Wang Y., Weaver F. A., Yu H. Human macrovascular endothelial cells: optimization of culture conditions In Vitro Cell Develop. Biol. Anim 2000 36, N 2:125–132.
[6] Chen C., Li J., Micko C. J., Pierce G. F., Cunningham M. R., Lumsden A. B. Cytotoxic effects of basic FGF and heparin binding EGF conjugated with cytotoxin saporin on vascular cell cultures J. Surg. Res 1998 75, N 1:35–41.
[7] Garmanchouk L. V., Pyaskovskaya O. N., Yanish Yu. V., Shlyakhovenko V. A., Dasyukevich O. I., Solyanik G. I. Influence of aconitine-containing herbal extract BC1 on proliferative and electrokinetic characteristics of endothelial cells. Exp. Oncol. 2005; 27, N 4:262–266.
[8] Gumcovski F., Kaminska G., Kaminski M., Morrisey L. W., Auerbach R. Heterogeneity of mouse vascular endothelium. In vitro studies of lymphatic, large blood vessel and microvascular endothelial cells. Blood Vessels. 1987; 24, N 1–2:11–23.
[9] Ivashchenko Yu. D., Gout I. T, Garmanchuk L. V., Osipova L. A. Purification of the epidermal growth factor with used HPLC. Exp. Oncol. 1985; 7, N 3: 46–49.
[10] Solyanik G. I., Pyaskovskaya O. N., Garmanchouk L. V. Cisplatin-resistant Lewis lung carcinoma cells possess increased level of VEGF secretion. Exp. Oncol 2003; 25, N 4:260–265.
[11] Alistratov A. V., Lisniyak I. A., Yatsenko S. M., Vinnitsky V. B. The dependence of VEGF level from characteristics of 3LL carcinoma development in C57Bl6 mice. Exp. Oncol. 2002; 24, N 1:64–68.
[12] Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxic assayas J. Immunol. Meth 1983 65, N 1–2:55–63.
[13] Garmanchuk L. V., Pyaskovskaya O. N., Vovyanko S. I., Plyushch G. I., Solyanik G. I. Vascular endothelial growth factor – prerogative of the actively proliferating endothelial cells IX Ukrainian biochemical conference (Kharkiv, 24–26 October, 2006) Kharkiv, 2006:88.
[14] Mooradian D. L., Diglio C. A. Effects of epidermal growth factor and transforming growth factor-beta 1 on rat heart endothelial cell anchorage-dependent and -independent growth Exp. Cell Res 1990 186, N 1:122–129.
[15] Semino C. E., Kamm R. D., Lauffenburger D. A. Autocrine EGF receptor activation mediates endothelial cell migration and vascular morphogenesis induced by VEGF under interstitial flow Exp. Cell Res 2006 312 N 3:289–298.
[16] Suhardja A., Hoffman H. Role of growth factors and their receptors in proliferation of microvascular endothelial cells Microsc. Res. Technol 2003 60, N 1:70–75.
[17] Tamama K., Fan V. H., Griffith L. G., Blair H. C., Wells A. Epidermal growth factor as a candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells Stem Cells 2006 24, N 3:686–695.
[18] Sini P., Wyder L., Schnell C., O'Reilly T., Littlewood A., Brandt R., Hynes N. E., Wood J. The antitumor and antiangiogenic activity of vascular endothelial growth factor receptor inhibition is potentiated by ErbB1 blockade Clin. Cancer Res 2005 11, N 12:4521–4532.
[19] Kerbel R., Folkman J. Clinical translation of angiogenesis inhibitors Nat. Rev. Cancer 2002 2, N 10:727–739.