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

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.