Cooperative Interactions Between Integrins and Growth Factor Signaling in Pathological Angiogenesis

As with most complex biological processes, angiogenesis requires the integration of a number of molecular signaling networks to coordinate multiple cues from both the extracellular tissue microenvironment as well as the cell’s interior. Thus an important area of angiogenesis investigation involves understanding the mechanisms that facilitate cooperation between multiple receptor–ligand signaling pathways. Two crucial networks that play active role in angiogenesis include growth factor/growth factor receptors and extracellular matrix/integrin receptor signaling systems. Emerging evidence suggests that these two important signaling systems depend in large part on each other, and function cooperatively to control new blood vessel development. Given the tissue-specific variations in the expression of components within each of these systems, significant challenges exist in order to exploit these signaling pathways for clinical intervention. A more detailed understanding of how the molecular components of these two signaling systems communicate with each other to direct and coordinate downstream effector functions may lead to optimized anti-angiogenic strategies to control malignant tumor progression. In this regard, we will discuss the multiple ways by which growth factor and integrin signaling pathways function cooperatively to regulate pathological angiogenesis within the context of the tissue microenvironment.