Angiopoietin 2 levels in sera of children with solid malignancies

Background: The Angiopoietins 1 and 2 (Ang1 and Ang2) are endothelial cell specific growth factors that act as ligands to the receptor Tie-2. Ang1 activates Tie-2, but the exact effect of Ang2 on the state of Tie-2 remains unclear. While Ang1 seems to play an important role in the remodeling of the primary vasculature in early development by promoting circumferential growth and stabilization of the vasculature, Ang2 apparently mediates a destabilizing signal and thus renders the vessels more plastic and susceptible to other angiogenic signals. In the adult organism, Ang2 expression is found wherever vascular remodeling takes place, hence also in the developing vasculature of tumors. Until now, the concentration of Ang2 in serum has been unknown.

Materials and Methods: Using the DuoSet ELISA Development Kit Ang2 (R&D Systems), we established an ELISA for the measurement of Angiopoietin 2 in serum with a intra-assay variation of 95±10% and an inter-assay variation of 99±18% (mean±SD). The sera of 66 patients, collected at the time of diagnosis, and 156 healthy controls were measured. The patient group consisted of children with a variety of solid malignancies, including Ewing's sarcoma, PNET, rhabdomyosarcoma, osteosarcoma, lymphoma, LHC, medulloblastoma, neuroblastoma, retinoblastoma, medulloblastoma, hepatoblastoma, nephroblastoma, hepatocellular carcinoma and adenocarcinoma. The control sera were collected from tumor-free children who had no ongoing infection or wound healing.

Results: The angiopoietin levels in the sera of our patients were 1103 pg/ml (median, range: 248–9612 pg/ml). The median of the control group was 678 pg/ml (range: 228–12075). The difference between patients' and controls' serum levels of Ang2 was significant (p=0.000) as determined by Mann Whitney U Test.

Conclusion: The established ELISA is a useful tool to further elucidate the role of Ang2 in the development of tumor vessels. The significant difference in the angiopoietin levels suggests a role of Angiopoietin 2 in the development of tumor vasculature in solid malignancies of childhood. Angiopoietin 2 might be a possible marker for tumor growth and angiogenesis.