1. ¹Microcirculation Research Group, University of Sheffield Medical School, Sheffield, S10 2RX, UK
2. ²Tumour Targeting Group, School of Medicine & Biomedical Sciences, University of Sheffield Medical School, Sheffield, S10 2RX, UK

Correspondence: Professor NJ Brown, Academic Unit of Surgical Oncology, University of Sheffield, Floor K, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. E-mail: n.j.brown@sheffield.ac.uk

Received 25 July 2005; Revised 11 November 2005; Accepted 11 November 2005; Published online 13 December 2005.

Abstract

An in vivo model has been established to study the role of macrophages in the initiation of angiogenesis by human breast tumour spheroids in vivo. The extent of the angiogenic response induced by T47D spheroids implanted into the dorsal skinfold chamber in nude mice was measured in vivo and compared to that induced by spheroids infiltrated with human macrophages prior to implantation. Our results indicate that the presence of macrophages in spheroids resulted in at least a three-fold upregulation in the release of vascular endothelial growth factor (VEGF) in vitro when compared with spheroids composed only of tumour cells. The angiogenic response measured around the spheroids, 3 days after in vivo implantation, was significantly greater in the spheroids infiltrated with macrophages. The number of vessels increased (macrophages vs no macrophages 341.9 vs 262.5, P<0.01), were shorter in length (macrophages vs no macrophages 1164.92 vs 1366.52, P<0.008) with an increased number of junctions (macrophages vs no macrophages 140.93 vs 111.25, P<0.025) all parameters indicative of new vessel formation. This is the first study to demonstrate a role for macrophages in the initiation of tumour angiogenesis in vivo.