Vesicular trafficking mechanisms in endothelial cells as modulators of the tumor vasculature and targets of antiangiogenic therapies

Abstract

A common feature of solid tumors is their ability to incite the formation of new blood and lymph vessels trough the processes of angiogenesis and lymphangiogenesis, respectively, to support tumor growth and favor metastatic dissemination. As a result of the lack of feedback regulatory control mechanisms or due to the exacerbated presence of pro-angiogenic signals within the tumor microenvironment, the tumor endothelium receives continuous signals to sprout and develop, generating vessels that are structurally and functionally abnormal. An emerging mechanism playing a central role in shaping the tumor vasculature is the endothelial-vesicular network that regulates trafficking/export and degradation of key signaling proteins and membrane receptors, including the vascular endothelial growth-factor receptor-2/3 and members of the Notch pathway. Here we will discuss recent evidence highlighting how vesicular trafficking mechanisms in endothelial cells contribute to pathological angiogenesis/lymphangiogenesis and can provide novel and exploitable targets in antiangiogenic therapies.

Keywords: angiogenesis; anticancer therapy; autophagy; cancer; endocytosis; pro-angiogenic signaling; vesicular trafficking.