Targeting Calcium Channels to Block Tumor Vascularization
Luca Munaron, Tullio Genova, Daniele Avanzato, Susanna Antoniotti and Alessandra Fiorio Pla
Affiliation: Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy.
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.
Keywords: Calcium channels, endothelial cells, tumor angiogenesis, tumor vascularization
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