Clinical usefulness of assessing VEGF and soluble receptors sVEGFR-1 and sVEGFR-2 in women with breast cancer
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Department of Laboratory Diagnostics, University of Medical Sciences, Poznan, Poland
Department and Clinic of Maxillofacial Orthopedies and Orthodontic, University of Medical Sciences, Poznan, Poland
Department of Oncological Surgery, Department of Oncology, University of Medical Sciences, Poznan, Poland
Corresponding author
Anna Thielemann   

Department of Laboratory Diagnostics, University of Medical Sciences, Poznan, Poland
Ann Agric Environ Med. 2013;20(2):293-297
The biological activity of VEGF depends on the presence of its specific receptors on the endothelial surface: VEGFR-1, VEGFR-2, and on their soluble forms sVEGFR-1 and sVEGFR-2. The binding of the membrane-bound receptors with VEGF affects the permeability, proliferation and migration of vascular endothelial cells. This creates the necessary conditions for the vascularisation of solid tumours and for the spread of remote metastases. The sVEGFR-1 and sVEGFR-2 receptors are believed to be natural inhibitors of VEGF.

To determine the clinical usefulness of VEGF and the sVEGFR-1 and sVEGFR-2 receptors level assay in women with primary breast cancer. The assessment also took into account: patient’s age, stage of the disease, histological grade, status of the axillary lymph nodes and size of the primary tumour.

Material and Methods:
The concentrations of VEGF, sVEGFR-1 and sVEGFR-2 were ascertained in 103 women with primary breast cancer. The concentrations of VEGF in the plasma, and those of the soluble receptors sVEGFR-1 and sVEGFR-2 in the serum, were assessed by ELISA, R&D Systems.

The study found significantly raised concentrations of VEGF, sVEGFR-1 and sVEGFR-2 in the serum of women with breast cancer, relative to the values obtained from the control group. It was found that with increasing clinical stages of the disease, the levels of VEGF and concentrations of sVEGFR-1 and sVEGFR-2 also increased. Similar findings were noted when assessing the degree of the histological grade of the tumours. Significantly higher values of VEGF protein and the assessed receptors were obtained from women with metastases to the axillary lymph nodes. A positive relationship, though without statistical significance, was noted between the concentration of sVEGFR-2 and the size of the tumour.

The high concentrations of the VEGF cytokine and the sVEGFR-1 and sVEGFR-2 receptors in women with breast cancer are responsible for giving rise to the processes of tumour angiogenesis. The concentrations of the VEGF protein and the soluble forms of the receptors sVEGFR-1 and sVEGFR-2 in the serum of breast cancer patients showed positive correlations with the clinical stage of the disease. These results point to the usefulness of VEGF assessment and its soluble receptors in the clinical evaluation of patients with breast cancer.

Barańska P, Jerczyńska H, Pawłowska Z. Vascular endothelial growth factor-structure and functions. Post Bioch. 2005; 51: 12–21.
Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nature Rev. 2002; 2: 795–803.
Esteva F J, Hortobagyi G N. Prognostic molecular markers in early breast cancer. Breast Cancer Res. 2004; 6: 109–118.
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, Ernst A de Bruijn. Vascular Endothelial Growth Factor and Angiogenesis. Pharmacol Rev. 2004; 56: 549–580.
Breier G. Functions of the VEGF/VEGF receptor system in the vascular system. Semin Thromb Hemost. 2000; 26: 553–559.
Barleon B, Reusch P, Totzke F, Herzog C, Keck C, Martiny-Baron G, Marmé D. Soluble VEGFR-1 secreted by endothelial cells and monocytes is present in human serum and plasma from healthy donors. Angiogenesis. 2001; 4: 143–154.
Neufeld G, Cohen T, Gengrinovitch S, Poltoraka Z. Vascular Endothelial Growth Factor (VEGF) and its receptor. Faseb J. 1999; 13: 9–22.
Bergler-Czop B, Brzezińska-Wcisło L, Syguła E. Evaluation of the nailfold skin capillaroscopic modifications of psoriatic patients and levels of the transforming growth factor α and vascular endothelial growth factor: an initiative paper. Post Dermatol Alergol. 2011; 28: 428–34.
McMahon G. VEGF Receptor Signaling in Tumor Angiogenesis. Oncologist. 2000; 5: 3–10.
Ferrara N, Gerber H.P, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003; 9: 669–676.
Horing C, Weich HA. Soluble VEGF receptors. Angiogenesis. 1999; 3: 33–39.
Rajkumar T. Growth factors and growth factor receptors in cancer. Curr Sci. 2001; 81: 535–541.
Shibuya M, Claesson-Welsh L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res. 2006; 312: 549–60.
Folkmann J. Angiogenesis-dependent diseases. Semin Oncol. 2001; 28: 536–542.
Bałan B, Słotwiński R. VEGF and tumor angiogenesis. Centr Eur J Immunol. 2008; 33: 232–236.
Wu H, Li Y, Zhu G, Zhang L, Zhang X, He X. Expression of vascular endothelial growth factor and its receptor (Flt-1) in breast carcinoma. Zhonghua Yi Xue Za Zhi 2002; 82: 708–711.
Hicklin DJ, Ellis LM. Role of the Vascular Endothelial Growth Factor Pathway in Tumor Growth and Angiogenesis. J Clin Oncol. 2005; 23: 1011–1027.
Murukesh N,Dive C, Jayson GC. Biomarkers of angiogenesis and their role in the development of VEGF inhibitors. Br J Cancer. 2010; 106: 8–18.
Otrock Z K, Makarem JA, Shamseddine AI.Vascular endothelial growth factor family of ligands and receptors: review. Blood Cells Mol Dis. 2007; 38: 258–268.
Li X, Claesson-Welsh, Shibuya M. VEGF receptor signal transduction. Methods Enzymol. 2008; 443: 261–284.
Korzeniewska M, Kołomecki K, Stępień H, Naze M, Stępień T, Kuzdak K. Assessement of pro-and antyangiogenic factors blood serum concentrations in patients with hormonal inactive adrenal tumors. Polish J Endocrinol. 2005; 1: 39–44.
Thielemann A, Kopczyński Z, Baszczuk A, Ćwiklińska K, Grodecka-Gazdecka S. Assessment of sVEGFR-1 concentration in patients with breast cancer. Współ Onkol. 2010; 14: 189–195.
Kumar H, Heer K, Greenman J, Kerin M, Monson J. Soluble FLT-1 is detectable in the sera of colorectal and breast cancer patients. Anticancer Res. 2002; 22: 1877–1880.
Toi M, Bando H, Ogawa T, Muta M, Hornig C, Weich HA. Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer. Int J Cancer. 2002; 98: 14–18.
Belgore FM, Lip GY, Bareford D. Plasma levels of vascular endothelial growth factor (VEGF) and its receptor, Flt-1, in haematological cancers: a comparison with breast cancer. Am J Hematol. 2001; 1(66): 59–61.
Gershtein ES, Scherbakov AM, Anurova OA, Krasilńikov MA, Kushlinsky NE. Phosphorylated Akt1 in human breast cancer measured by direct sandwich enzyme-linked immunosorbent assay: Correlation with clinicopathological features and tumor VEGF-signaling system component levels. Int J Biol Markers. 2006; 21: 12–19.
Benoy I, Salgado R, Colpaert C. Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients. Clin Breast Cancer. 2002; 1: 311–316.
Fuhrmann-Benzakein H, Ma-HN, Rubba-Brandt L. Elevated levels of angiogenic cytokines in the plasma of cancer patients. Int J Cancer. 2000; 1: 40–45.
Rmali KA, Puntis MCA, Jiang W. Level of the expression of VEGF-A, B, C, D and their receptors (FLT-1, KDR and FLT-4) and its correlation with prognosis in patients with colorectal cancer. Int Cancer Res. 2006; 2: 31–34.
Meunier- Carpentier S, Dales JP, Djemli A, Garcia S, Bonnier P, Andrac-Meyer L, Lavaut MN, Allasia C. Comparison of the prognosis indication of VEGFR-1 and VEGFR-2 and Tie2 receptor expression in breast carcinoma. Int J Oncol. 2005; 26: 977–984.
Chang YT, Chang MC, Wei SC, Tien YW, Hsu C, Liang PC et al. Serum vascular endothelial growth factor/soluble vascular endothelial growth factor receptor 1 ratio is an independent prognostic marker in pancreatic cancer. Pancreas 2008; 82: 8124-1837.
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