title: 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.
authors.affiliation: Cell Death Research & Therapy (CDRT) Unit, Department of Cellular and Molecular Medicine, KU Leuven University of Leuven, Belgium.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Maes
authors.affiliation: Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Olmeda
authors.affiliation: Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: María S
authors.initials: MS
authors.lastname: Soengas
authors.affiliation: Cell Death Research & Therapy (CDRT) Unit, Department of Cellular and Molecular Medicine, KU Leuven University of Leuven, Belgium.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agostinis
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors
keywords: angiogenesis; anticancer therapy; autophagy; cancer; endocytosis; pro-angiogenic signaling; vesicular trafficking