The role of the tumor microenvironment in regulating angiogenesis

Abstract

The tumor microenvironment plays a crucial role in cancer development and progression. Paracrine signaling between tumor cells and the nonneoplastic, genetically normal, cells that make up the microenvironment is a critical component influencing the progression of tumors from the in situ stage to metastatic disease. Despite the importance of these paracrine signaling mechanisms and factors, the vast majority of academic research and development in the pharmaceutical industry is still targeted toward mutations and aberrant signaling pathways within tumor cells. As a result, the intercellular signaling between tumor cells and the microenvironment has not been as extensively studied with regard to the regulation of angiogenesis. In this chapter we define the key players in the regulation of angiogenesis and examine how their expression is regulated in the microenvironment. The resulting analysis presents observations that at first glance may seem paradoxical. However, these nuances serve to underscore the complexity of interactions and the need to better delineate and define the environmental context underlying these mechanisms.