The purinergic signaling interfaces in breast cancer angiogenesis

Cancer is a group of diseases characterized by disordered cell proliferation and loss of tissue architecture. Breast cancer (BC) is the most common and lethal cancer among women, standing out for its molecular, histological and pathological heterogeneity. The BC tumor microenvironment (TME) is a complex ecosystem comprising transformed cells and a multitude of non-tumor cells, embedded in an altered extracellular matrix. Endothelial cells are present, driving angiogenesis, a relevant hallmark that ensures nutrition and oxygenation through the formation of new blood vessels. During this process, a complex network of molecules is released by tumor and endothelial cells, such as Vascular Endothelial Growth Factor (VEGF), that, in turn, induce cancer progression, diffusion, and metastasis. Purinergic signaling also regulates the functioning of endothelial cells involving the action of purines (ATP, ADP, UTP, UDP and adenosine) as signaling in purinergic receptors, with their concentration modulated by enzymes known as ectonucleotidases. This review aims to explore the contribution of purinergic signaling to BC angiogenesis, highlighting potential therapeutic targets currently under scientific focus. In general, the TME presents overexpression of ATP and adenosine, which stimulate endothelial cells through purinergic receptors. This stimulus promotes the formation of new vessels, mainly via the release of VEGF. Thus, purinergic signaling emerges as a central mechanism in BC angiogenesis, with potential to be explored in the development of antitumor therapies.