Skip to main content

Advertisement

SpringerLink
Log in

A decreased ratio between serum levels of the antagonistic angiopoietins 1 and 2 indicates tumour progression of malignant melanoma

  • Short Communication
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

The growth of solid tumours like malignant melanoma depends on the ability of neoplastic cells to induce angiogenesis to ensure sufficient supply with nutrients and oxygen. The process of angiogenesis is tightly controlled by positive and negative regulators. Since many of these factors can be measured in the serum of patients, their use as tumour markers has been suggested. The angiopoietins 1 and 2 have been demonstrated to be secreted by various tumour cells. By binding to the Tie-2 receptor on endothelial cells, they regulate angiogenesis. Whereas angiopoietin-1 maintains quiescence of vessels, angiopoietin-2 increases angiogenesis by destabilising vessels and sensitising them to the effect of growth factors of the VEGF family. Since both angiopoietins compete for the same Tie-2 receptor and cause opposite effects concerning angiogenesis, the ratio between these two ligands is crucial. Therefore, we have measured serum levels of both angiopoietins in the serum of 148 melanoma patients at different stages of disease. Whereas angiopoietin-1 levels did not change during disease progression, angiopoietin-2 levels were significantly higher in advanced stage disease. Compared to the established tumour-marker S100B, angiopoietin-2 levels or the ratio between both angiopoietins did not show increased sensitivity for the early detection of advanced stages of malignant melanoma. In conclusion, the ratio between both angiopoietins is significantly altered in late stage melanoma patients, shifting the balance to favour angiogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Acland K, Evans AV, Abraha H, Healy CM, Roblin P, Calonje E, Orchard G, Higgins E, Sherwood R, Russell-Jones R (2002) Serum S100 concentrations are not useful in predicting micrometastatic disease in cutaneous malignant melanoma. Br J Dermatol 146(5):832–835

    Article  PubMed  CAS  Google Scholar 

  2. Augustin HG, Koh GY, Thurston G, Alitalo K (2009) Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 10(3):165–177

    Article  PubMed  CAS  Google Scholar 

  3. Bach F, Uddin FJ, Burke D (2007) Angiopoietins in malignancy. Eur J Surg Oncol 33(1):7–15

    Article  PubMed  CAS  Google Scholar 

  4. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27(36):6199–6206

    Article  PubMed  Google Scholar 

  5. Deichmann M, Benner A, Bock M, Jackel A, Uhl K, Waldmann V, Naher H (1999) S100-Beta, melanoma-inhibiting activity, and lactate dehydrogenase discriminate progressive from nonprogressive American Joint Committee on Cancer stage IV melanoma. J Clin Oncol 17(6):1891–1896

    PubMed  CAS  Google Scholar 

  6. Fukuhara S, Sako K, Noda K, Zhang J, Minami M, Mochizuki N (2010) Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis. Histol Histopathol 25(3):387–396

    PubMed  CAS  Google Scholar 

  7. Garbe C, Leiter U, Ellwanger U, Blaheta HJ, Meier F, Rassner G, Schittek B (2003) Diagnostic value and prognostic significance of protein S-100beta, melanoma-inhibitory activity, and tyrosinase/MART-1 reverse transcription-polymerase chain reaction in the follow-up of high-risk melanoma patients. Cancer 97(7):1737–1745

    Article  PubMed  CAS  Google Scholar 

  8. Helfrich I, Edler L, Sucker A, Thomas M, Christian S, Schadendorf D, Augustin HG (2009) Angiopoietin-2 levels are associated with disease progression in metastatic malignant melanoma. Clin Cancer Res 15(4):1384–1392

    Article  PubMed  CAS  Google Scholar 

  9. Huang H, Bhat A, Woodnutt G, Lappe R (2010) Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev Cancer 10(8):575–585

    Article  PubMed  CAS  Google Scholar 

  10. Kurschat P, Eming S, Nashan D, Krieg T, Mauch C (2007) Early increase in serum levels of the angiogenesis-inhibitor endostatin and of basic fibroblast growth factor in melanoma patients during disease progression. Br J Dermatol 156(4):653–658

    Article  PubMed  CAS  Google Scholar 

  11. Lobov IB, Brooks PC, Lang RA (2002) Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci USA 99(17):11205–11210

    Article  PubMed  CAS  Google Scholar 

  12. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277(5322):55–60

    Article  PubMed  CAS  Google Scholar 

  13. Park JH, Park KJ, Kim YS, Sheen SS, Lee KS, Lee HN, Oh YJ, Hwang SC (2007) Serum angiopoietin-2 as a clinical marker for lung cancer. Chest 132(1):200–206

    Article  PubMed  CAS  Google Scholar 

  14. Pichiule P, Chavez JC, LaManna JC (2004) Hypoxic regulation of angiopoietin-2 expression in endothelial cells. J Biol Chem 279(13):12171–12180

    Article  PubMed  CAS  Google Scholar 

  15. Shim WS, Ho IA, Wong PE (2007) Angiopoietin: a TIE(d) balance in tumor angiogenesis. Mol Cancer Res 5(7):655–665

    Article  PubMed  CAS  Google Scholar 

  16. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87(7):1171–1180

    Article  PubMed  CAS  Google Scholar 

  17. Tait CR, Jones PF (2004) Angiopoietins in tumours: the angiogenic switch. J Pathol 204(1):1–10

    Article  PubMed  CAS  Google Scholar 

  18. Thomas M, Augustin HG (2009) The role of the angiopoietins in vascular morphogenesis. Angiogenesis 12(2):125–137

    Article  PubMed  CAS  Google Scholar 

  19. Ugurel S, Rappl G, Tilgen W, Reinhold U (2001) Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival. J Clin Oncol 19(2):577–583

    PubMed  CAS  Google Scholar 

  20. Utikal J, Schadendorf D, Ugurel S (2007) Serologic and immunohistochemical prognostic biomarkers of cutaneous malignancies. Arch Dermatol Res 298(10):469–477

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the German Research Foundation DFG to P.K. (SFB 829, project B5).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Dermatology and Venerology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany

    Masyar Gardizi, Anna Riese, Thomas Krieg, Cornelia Mauch & Peter Kurschat

  2. Department of Nephrology, University Hospital of Cologne, Cologne, Germany

    Christine Kurschat

  3. Institute of Medical Statistics, Informatic and Epidemiology (IMSIE), University Hospital of Cologne, Cologne, Germany

    Moritz Hahn

Authors
  1. Masyar Gardizi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christine Kurschat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Riese
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Moritz Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Krieg
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cornelia Mauch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter Kurschat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Kurschat.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 21 kb)

Supplementary material 2 (PDF 122 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gardizi, M., Kurschat, C., Riese, A. et al. A decreased ratio between serum levels of the antagonistic angiopoietins 1 and 2 indicates tumour progression of malignant melanoma. Arch Dermatol Res 304, 397–400 (2012). https://doi.org/10.1007/s00403-012-1228-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-012-1228-2

Keywords

Search

Navigation