Chapter 1. Introducion, How tumor-endothelial cell communication within the tumor microenvironment affects angiogenesis

AAngiogenesis, the formation of new blood vessels from preexisting ones, occurs when the high proliferation rate of cancer cells creates hypoxic zones in the tumor mass and influences the progression of tumors since it guarantees the oxygen and nutrient delivery and an efficient way for neoplastic cells to reach the bloodstream and metastasize. Tumor neovascularization is the result of an angiogenic switch, meaning the unbalance between pro- and antiangiogenic factors, in favor of the first ones. The majority of the angiogenesis modulators acting on endothelial cells derive from neoplastic cells, but a growing contribution is coming from other cells of the tumor microenvironment as cancer-associated fibroblasts, pericytes, macrophages and immune cells. On their site, tumor endothelial cells communicate with the other cellular components in favor of tumor progression. In this chapter the description of the major proangiogenic factors is provided together with the one on antiangiogenic molecules. The transcriptional and not transcriptional mechanisms responsible for their accumulation or downregulation are reported. The signaling pathways depending on the receptor (and coreceptor) activation are described. All these findings have allowed the development of antiangiogenic strategies, but at the same time may explain the mechanisms of antiangiogenic drug failure and resistance.