Endothelial-stromal interactions in angiogenesis

Abstract

Purpose of review: Angiogenesis often occurs in the context of a wound or tumor stroma. This review will focus on the recent findings on the interactions between angiogenic endothelial cells and the other components of the stroma - fibroblasts, pericytes and extracellular matrix.

Recent findings: Large-scale gene expression arrays have provided a remarkable insight into the diversity of fibroblasts in different tissues and under different conditions. These somewhat neglected cells are now understood to play a critical role in tumor growth, regulating not only the phenotype of the tumor cells but also the angiogenic response that supports them. These advances are leading to an understanding of the soil and seed hypothesis at the molecular level. In addition, there is a new focus on the role of pericytes in regulating angiogenesis and their potential as targets for tumor therapy.

Summary: Initiation of new blood vessel formation requires metalloproteinase induction leading to the degradation of the basement membrane, sprouting of endothelial cells and regulation of pericyte attachment. Fibroblasts and their activated counterpart, the myofibroblast, play a large role in synchronizing these events through the expression of numerous extracellular matrix molecules, growth factors and morphogens, including fibroblast growth factors and transforming growth factor beta.