title: Targeting calcium channels to block tumor vascularization.
abstract: Blood vessels and endothelial cells (ECs) are highly versatile in order to accomplish local tissutal needs in the physiological and pathological conditions. Tumor vasculature, in particular, exhibits special morphological and functional features, partly due to the peculiarity of tumor-derived ECs (TECs). This is of great importance for the discovery of selective molecular targets potentially suitable to interfere with tumor growth and spread. In normal ECs, proangiogenic calcium signaling is mediated by different calcium channels, mainly TRPs and Orai, that could play a pivotal role in physiological angiogenesis. They are regulated through multiple mechanisms, involving their interaction with bioactive lipids (arachidonic acid and its metabolites), nitrosylation, sulfhydration, phosphorylation, cytoskeleton-mediated membrane trafficking, and calcium stores depletion. On the other hand, proangiogenic calcium events in TECs have been investigated only recently and their characterization is still preliminary. ECs obtained from human breast and renal carcinomas (B-TECs and R-TECs respectively) display altered calcium signals, which are associated with modified expression and function of TRP channels. Here, we review the state of the art in the field of calcium signaling and tumor vascularization, the related recent literature and patents. Finally, we provide some suggestions for future developments.
authors.affiliation: Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy. luca.munaron@unito.it
authors.forename: Luca
authors.initials: L
authors.lastname: Munaron
authors.forename: Tullio
authors.initials: T
authors.lastname: Genova
authors.forename: Daniele
authors.initials: D
authors.lastname: Avanzato
authors.forename: Susanna
authors.initials: S
authors.lastname: Antoniotti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fiorio Pla
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D015195:Drug Design; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007880:Legislation, Drug; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*; D010330:Patents as Topic
chemical_list: D020533:Angiogenesis Inhibitors; D002121:Calcium Channel Blockers; D015220:Calcium Channels