Differential effects of ionizing radiation on angiogenesis and matrix metalloproteinases (MMPs) activity in vitro and in vivo

Abstract

Purpose: Recently, radiation has been used in combination with anti-angiogenic molecules to assess synergistic anti-tumor activity. While studies have provided some understanding of the effects of ionizing radiation on cells, the biochemical and molecular mechanisms contributing to radiation-induced alterations in cellular behavior are still not completely understood. Importantly, previous studies have indicated that ionizing radiation can regulate cellular processes such as gene expression, cell adhesion and migration, all of which are crucial events in angiogenesis and tumor growth. In fact, ionizing radiation has been suggested to regulate the expression of matrix degrading proteases including members of matrix metalloproteinase (MMP) family. Proteolytic remodeling of the extracellular matrix (ECM) is thought to play a critical role in regulating both angiogenesis as well as well tumor invasion. Thus, a more complete understanding of the molecular and biochemical impact of ionizing radiation on the structure and function of individual angiogenesis regulatory proteins may provide new insight into optimization and utilization of radiation therapy for treating cancer and neovascular diseases.