Angiogenic role for glycodelin in tumorigenesis

Angiogenesis plays an important role in neovascularization in tumors. Glyco delin, a hormone-responsive protein, has been detected in tumors of reprodu ctive organs and is found in high levels in the plasma of subjects with gyn ecological malignancies. Glycodelin is also found in the endothelial cells of the umbilical cord and in the blood vessels of tumors. In this study, we tested whether glycodelin-rich amniotic fluid and a synthetic peptide deri ved from the sequence of glycodelin peptide (Gp) might promote angiogenic r esponse by examining the migration and tube formation in human umbilical co rd vein endothelial cells (HUVECs). Increased migration and tube formation of HUVECs were found in the presence of amniotic fluid and Gp, and this inc rease was blocked by antibody to Gp and by an anti-vascular endothelial gro wth factor (VEGF) antibody, suggesting that the angiogenic effects of glyco delin might be mediated by VEGF. The results also showed that Gp significan tly increased the release of VEGF protein and mRNA expression in HUVECs, RL -95 (human endometrial carcinoma cells), OVCAR-3 (human ovarian adenocarcin oma cells), EM42 (human endometrial epithelial cells), THP-1 (human monocyt e), and MCF-7 and MDA-MB-231 (human breast adenocarcinoma cells) cell lines . VEGF receptor Fit-1 mRNA expression in HUVECs was also increased in the p resence of Gp. These findings, together with the suggestion from the litera ture that glycodelin may have immunosuppressive properties, suggest that gl ycodelin might play an important role in neovascularization during embryoge nesis and tumor development.