Expression and function of angiopoietin-1 in breast cancer

Angiopoietin-1 (Ang1) has been shown to act as an angiogenic promoter in em bryonic angiogenesis by promoting vascular branching, pericyte recruitment and endothelial survival, We have investigated the role of Ang1 in tumour n eovascularization under clinical conditions and in animal models. The expre ssion of Ang1 in clinical breast cancer specimens was analysed by using las er-capture microdissection and reverse transcriptase-linked polymerase chai n reaction (RT-PCR) on RNA isolated from the samples. Despite the expressio n of Ang1 in many human breast cancer cell lines, the gene was expressed in only three of 21 breast cancer clinical specimens, even though its recepto r, Tie2, is abundant in the vasculature of all of these tumours. Ang1 was t hen overexpressed in a human breast cancer cell line (MCF-7) on its own and in conjunction with FGF1, an angiogenic factor shown to be able to increas e the tumorigenicity of MCF-7 cells. High concentrations of Ang1 were produ ced in the conditioned media of the transfected cells (range 156-820 ng ml( -1)). However, in contrast to its physiological role as promoter of angioge nesis, overexpression of Ang1 did not enhance tumour growth, but instead ca used up to a 3-fold retardation of tumour growth (P = 0,003). (C) 2000 Canc er Research Campaign.