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Circulating levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-3 (MMP-3), and BCL-2 in malignant melanoma

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Abstract

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis that stimulates proliferation, migration, and metastasis of melanoma. In literature, all studies concerning influences of matrix metalloproteinases (MMPs) and antiapoptotic proteins on VEGF-induced angiogenesis in melanoma patients have been performed in tissue scale in melanoma. The objective of this study was to determine the value of circulating serum VEGF and its possible mechanisms of angiogenesis by circulating VEGF, MMP-3, and Bcl-2 in patients with melanoma. Fifty-one patients with cutaneous melanoma pathologically verified at different stages, and eighteen healthy controls were investigated. Serum VEGF, MMP-3, and Bcl-2 levels were quantitatively analyzed by ELISA. The serum VEGF (P = 0.034) and Bcl-2 (P = 0.005) levels were significantly higher in patients with melanoma than in the control group. However, there was no significant difference in the serum MMP-3 level between melanoma patients and controls (P = 0.51). The serum levels of VEGF were significantly influenced only by Breslow thickness (P = 0.045) and mitosis (0.039) and were not positively correlated with the stage of the disease. Among serum parameters, a significant relationship was found only between serum levels of VEGF and MMP-3 (r = 0.32, P = 0.023). In conclusion, our study demonstrates increased concentrations of VEGF and Bcl-2, but not MMP-3, in serum of melanoma patients regardless of the stage of the disease. VEGF may be a potential endothelial cell growth and survival factor. The mechanism of VEGF regulation of angiogenesis may be in part due to enhanced proliferation and survival of endothelial cells by differential expression of antiapoptotic genes and in part by activation of MMPs.

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References

  1. Poon RT, Fan ST, Wong J. Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol. 2001;19:1207–25.

    PubMed  CAS  Google Scholar 

  2. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–27.

    Article  PubMed  CAS  Google Scholar 

  3. Salven P, Heikkila P, Joensuu H. Enhanced expression of vascular endothelial growth factor in metastatic melanoma. Br J Cancer. 1997;76:930–4.

    PubMed  CAS  Google Scholar 

  4. Claffey KPM, et al. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res. 1996;56:172–81.

    PubMed  CAS  Google Scholar 

  5. Simonetti O, et al. Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions. Cancer. 2002;95(9):1963–70.

    Article  PubMed  CAS  Google Scholar 

  6. Viac J, Schmitt D, Claudy A. Circulating vascular endothelial growth factor (VEGF) is not a prognostic indicator in malignant melanoma. Cancer Lett. 1998;125:35–8.

    Article  PubMed  CAS  Google Scholar 

  7. Redondo P, Bandres E, Solano T, Okroujnov I, Garcia-Foncillas J. Vascular endothelial growth factor (VEGF) and melanoma. N-Acetylcysteine downregulates VEGF production in vitro. Cytokine. 2000;12:374–8.

    Article  PubMed  CAS  Google Scholar 

  8. Ugurel S, Rappl G, Tilgen W, Reinhold U. Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival. J Clin Oncol. 2001;19:577–83.

    PubMed  CAS  Google Scholar 

  9. Redondo P, et al. Immunologic escape and angiogenesis in human malignant melanoma. J Am Acad Dermatol. 2003;49:255–63.

    Article  PubMed  Google Scholar 

  10. Pelletier F, et al. Circulating vascular endothelial growth factor in cutaneous malignant melanoma. Br J Dermatol. 2005;152:685–9.

    Article  PubMed  CAS  Google Scholar 

  11. Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. Natl Cancer Inst. 1997;89:1260–70.

    Article  CAS  Google Scholar 

  12. McCawley LJ, Matrisian LM. Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol Med Today. 2000;6:149–56.

    Article  PubMed  CAS  Google Scholar 

  13. Burbridge MF, et al. The role of the matrix metalloproteinases during in vitro vessel formation. Angiogenesis. 2002;5:215–26.

    Article  PubMed  CAS  Google Scholar 

  14. Nör J, Christensen J, Mooney DJ, Polverini PJ. Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of bcl-2 expression. Am J Pathol. 1999;154:375–84.

    PubMed  Google Scholar 

  15. Nör JE, et al. Up-regulation of Bcl-2 in microvascular endothelial cells enhances intratumoral angiogenesis and accelerates tumor growth. Cancer Res. 2001;61:2183–8.

    PubMed  Google Scholar 

  16. Liu W, et al. Endothelial cell survival and apoptosis in the tumor vasculature. Apoptosis. 2000;5:323–8.

    Article  PubMed  CAS  Google Scholar 

  17. Gerber HP, Dixit V, Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem. 1998;273:13313–6.

    Article  PubMed  CAS  Google Scholar 

  18. Tran J, et al. Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells. Biochem Biophys Res Commun. 1999;264:781–8.

    Article  PubMed  CAS  Google Scholar 

  19. Iervolino A, et al. Bcl-2 overexpression in human melanoma cells increases angiogenesis through VEGF mRNA stabilization and HIF-1-mediated transcriptional activity. FASEB J. 2002;16:1453–5.

    PubMed  CAS  Google Scholar 

  20. Segura I. Inhibition of programmed cell death impairs in vitro vascular-like structure formation and reduces in vivo angiogenesis. FASEB J. 2002;16:833–41.

    Article  PubMed  CAS  Google Scholar 

  21. Tas F, et al. Serum bcl-2 and survivin levels in melanoma. Melanoma Res. 2004;14:543–6.

    Article  PubMed  CAS  Google Scholar 

  22. Tas F, et al. Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in patients with malignant melanoma. Med Oncol. 2005;22:39–44.

    Article  PubMed  CAS  Google Scholar 

  23. Howell WM, Bateman AC, Turner SJ, Collins A, Theaker JM. Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma. Genes Immun. 2002;3:229–32.

    Article  PubMed  CAS  Google Scholar 

  24. Walker RA, Woolley DE. Immunolocalisation studies of matrix metallproteinase-1, -2, and -3 in human melanoma. Virchows Arch. 1999;435:574–9.

    Article  PubMed  CAS  Google Scholar 

  25. Hofmann UB, et al. Matrix metalloproteinases in human melanoma cell lines and xenografts: increased expression of activated matrix metalloproteinase-2 (MMP-2) correlates with melanoma progression. Br J Cancer. 1999;81:774–82.

    Article  PubMed  CAS  Google Scholar 

  26. Meric JB, et al. Relevance of matrix metalloproteinase (MMP) plasma levels in malignant melanoma (MMM). Proc Am Soc Clin Oncol. 2003;22:721, Abstract 2899.

    Google Scholar 

  27. Leiter U, Schmid RM, Kaskel P, Peter RU, Krahn G. Antiapoptotic bcl-2 and bcl-XL in advanced malignant melanoma. Arch Dermatol Res. 2000;292:225–32.

    Article  PubMed  CAS  Google Scholar 

  28. Gradilone A, et al. Survivin, bcl-2, bax, and bcl-X gene expression in sentinal lymph nodes from melanoma patients. J Clin Oncol. 2003;21:306–12.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Faruk Tas.

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Tas, F., Duranyildiz, D., Oguz, H. et al. Circulating levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-3 (MMP-3), and BCL-2 in malignant melanoma. Med Oncol 25, 431–436 (2008). https://doi.org/10.1007/s12032-008-9058-y

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  • DOI: https://doi.org/10.1007/s12032-008-9058-y

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