ETA receptor antagonist may have antiangiogenic role.(endothelin)

2002 OCT 17 - (NewsRx.com & NewsRx.net) -- Cancer researchers in Italy have reported study findings that suggest specific endothelin-1 receptor antagonists could have a therapeutic role in preventing ovarian cancer tumor angiogenesis and cell growth.

"Angiogenesis is an essential prerequisite for tumor growth, invasion, and metastasis," noted F. Spinella and colleagues, Regina Elena Institute of Cancer Research. "In ovarian carcinoma cells, endothelin-1 (ET-1) stimulates the secretion of vascular endothelial growth factor (VEGF), a major mediator of tumor angiogenesis.

"In OVCA 433 and HEY ovarian carcinoma cell lines, ET-1 treatment increases VEGF mRNA expression and induces VEGF protein levels in a time- and dose-dependent fashion, and do so to a greater extent under hypoxic conditions. ET-1 also increases hypoxia-inducible factor-1alpha (HIP-1alpha) accumulation and activates the HIP-1 transcription complex under both normoxic and hypoxic conditions, suggesting a role for HIP-1 in the induction of VEGF expression. These effects are inhibited by the selective ETA receptor (ETAR) antagonist, BQ123," the researchers explained.

"The ET-1-induced increase in HIP-1alpha protein levels is due to the enhanced HIP-1alpha stabilization," Spinella and colleagues said.

They concluded that their "results implicate ...