Raised plasma endostatin levels correlate inversely with breast cancer angiogenesis

Abstract

Background Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgical removal of breast tumors on plasma endostatin and vascular endothelial growth factor (VEGF) levels was evaluated. Tumor tissues were analyzed for expression of Intratumoral microvessel density (IMVD) and endostatin. The effect of VEGF and endostatin in inducing apoptosis on human liver microvascular endothelial cells (HLMVEC) was investigated. Materials and methods Plasma from healthy volunteers, patients with fibroadenomas and breast cancer patients were assayed for endostatin and VEGF via immunoassay, pre-operatively and four weeks post-operatively. Expression of endostatin in tumor tissue was determined by Western blotting. IMVD was assessed following immunohistochemical staining with anti-CD34 antibody. Results Plasma endostatin levels, in breast cancer patients, were significantly elevated ( P = 0.015) in the post-operative (60.59 ± 7.70 ηg/ml) compared with the pre-operative group (30.62 ± 4.54 ηg/ml) and with normal age-matched controls (34.97 ± 3.76 ηg/ml). In patients with high pre-operative plasma endostatin value, IMVD was decreased to 20.1 ± 3.2 counts compared with 41.9 ± 5.4 counts in those with low pre-operative endostatin value ( P = 0.006). Neither plasma endostatin nor VEGF levels correlated with routine clinico-pathological parameters. Endostatin induced endothelial cell apoptosis and modulated the cytoprotective effect of VEGF in HLMVEC survival. Conclusion Plasma endostatin levels are increased in patients following surgical removal of the primary tumor. The decreased IMVD seen in patients with higher endostatin levels may be due to the apoptosis-inducing effect of endostatin on microvascular endothelial cells.