Newcastle disease virus suppresses angiogenesis in mammary adenocarcinoma models

Abstract

Cancer cells heavily utilise angiogenesis process to increase vascularisation for tumour mass growth and spread, so targeting this process is important to create an effective therapy. The AMHA1 strain of Newcastle disease virus (NDV) is an RNA virus with natural oncotropism. NDV induces direct tumour cytolysis, apoptosis, and immune stimulation. This work aimed to test NDV anti-angiogenic activity in a breast cancer model. To evaluate NDV’s antitumour effect in vivo, NDV was tested against mammary adenocarcinoma AN3 transplanted in syngeneic immunocompetent mice. In vivo antiangiogenic activity was evaluated by quantifying the blood vessels in treated and control tumour sections. In vitro experiments that exposed AMN3 mammary adenocarcinoma cells and Hep-2 laryngeal carcinoma cells to NDV at different time intervals were performed to identify the exact mechanism of anti-angiogenesis by using angiogenesis microarray slides. In vivo results showed significant tumour regression and significant decrease in blood vessel formation in treated tumour sections. The in vitro microarray analysis of 14 different angiogenesis factors revealed that NDV downregulated angiopoietin-1, angiopoietin-2, and epidermal growth factor in mammary adenocarcinoma cells. However, NDV elicited a different effect on Hep-2 as represented by the downregulation of inducible protein 10, intracellular adhesion molecule-1, and basic fibroblast growth factor beta in NDV-infected tumour cells. It was found out that microarray analysis results helped interpret the in vivo data. The results suggested that the NDV oncolytic strain reduced angiogenesis by interfering with angiogenesis factors that might reduce tumour cell proliferation, infiltration, and invasion.