title: A decreased ratio between serum levels of the antagonistic angiopoietins 1 and 2 indicates tumour progression of malignant melanoma.
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.
authors.affiliation: Department of Dermatology and Venerology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
authors.forename: Masyar
authors.initials: M
authors.lastname: Gardizi
authors.forename: Christine
authors.initials: C
authors.lastname: Kurschat
authors.forename: Anna
authors.initials: A
authors.lastname: Riese
authors.forename: Moritz
authors.initials: M
authors.lastname: Hahn
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.forename: Peter
authors.initials: P
authors.lastname: Kurschat
mesh_terms: D042683:Angiopoietin-1 / Q000097:blood*; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000097:blood* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood; D018450:Disease Progression; D006801:Humans; D008545:Melanoma / Q000097:blood* / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000097:blood; D009414:Nerve Growth Factors / Q000097:blood; D042787:Receptor, TIE-2 / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D012878:Skin Neoplasms / Q000097:blood* / Q000098:blood supply*
chemical_list: C467630:ANGPT1 protein, human; C117578:ANGPTL1 protein, human; D042683:Angiopoietin-1; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D014408:Biomarkers, Tumor; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D042787:Receptor, TIE-2