Extracellular influences on tumour angiogenesis in the aged host

Abstract

Whether tumours are epithelial or non-epithelial in origin, it is generally accepted that once they reach a certain size all solid tumours are dependent upon a vascular supply to provide nutrients. Accordingly, there is great interest in how the extracellular environment enhances or inhibits vascular growth. In this minireview, we will examine key extracellular components, their changes with ageing, and discuss how these alterations may influence the subsequent development of tumour vasculature in the aged host. Because of the tight correlation between advanced age and development of prostate cancer, we will use prostate cancer as the model throughout this review.

Figure 1

Effects of the aging microenvironment on angiogenesis of prostate tumours. The presence of senescent cells increases with age. These cells alter their expression of ECM proteins, which in turns modifies the composition of the microenvironment. Although the stromal cell has not been shown to senesce in the prostate, the cytokines produced by senescent epithelium influence stromal cell function and secretions. Local increases in hormones, growth factors (such as IGF-1), and matricellular proteins such as thrombospondin (TSP1) further alter the microenvironment. The aged prostate microenvironment, therefore, contains many components that are pro-angiogenic, thus supporting the growth of transformed epithelial cells and enhancing angiogenesis of the primary tumour in the aged host.