Primary tumor dependent inhibition of tumor growth, angiogenesis, and perfusion of secondary breast cancer in bone

Abstract

The systemic balance of angiogenic and anti-angiogenic factors has been proposed to play a key-role in primary tumor growth dependent growth suppression of secondary tumors. Despite the importance of the organ microenvironment to angiogenesis and microcirculation, the influence of a primary tumor on secondary bone tumors has not been investigated so far. Since breast cancer has a high propensity to spread to bone, we used an in vivo xenograft model to determine the impact of growing breast cancer cells (MCF-7) in the mammary fat pad on the microvascular properties of subsequently inoculated secondary breast cancer tumors in bone. Mice were either treated with a resection of the primary tumor (n = 10) or no surgery (n = 9) and intravital microscopy was performed over 25 days in bone tumors. Tumor growth in bone was temporarily suppressed by the primary tumor on days 10 and 14. While microvascular permeability and vascular diameter decreased in both groups over time, the presence of the primary tumor was accompanied by a decreased tumor perfusion on days 8 and 10 through a reduction in vessels with diameters between 5 and 20 µm. The results imply a potential benefit of a therapeutic regime in which the resection of the primary tumor is combined with an anti-angiogenic therapy in the perioperative or direct postoperative period. This might result in reduced progression of bone metastasis subsequent to excision of the primary tumor.