Systems biology of ion channels and transporters in tumor angiogenesis: An omics view

Solid tumors require the formation of new blood vessels to support their growth, invasiveness and metastatic potential. Tumor neovascularization is achieved by vasculogenesis from endothelial precursors and by sprouting angiogenesis from preexisting vessels. The complex sequence of events driving these processes, including endothelial activation, proliferation, migration and differentiation, is associated with fluxes of ions, water and other small molecules mediated by a great pool of ion channels and transporters (ICT). This 'transportome' is regulated by environmental factors as well as intracellular signaling molecules. In turn, ICT play a prominent role in the response to angiogenesis-related stimuli through canonical and 'unconventional' activities: indeed, there is an increasing recognition of the multifunctionality of several ion channels that could also be annotated as receptors, enzymes, scaffolding proteins, mechanical and chemical sensors. The investigation of ICT structure and function has been far from the experimental oncology for long time and these two domains converged only very recently. Furthermore, the systems biology viewpoint has not received much attention in the biology of cancer transportome. Modulating angiogenesis by interference with membrane transport has a great potential in cancer treatment and the application of an 'omics' logic will hopefully contribute to the overall advancement in the field. This review is an attempt to apply the systems biology approach to the analysis of ICT involved in tumor angiogenesis, with a particular focus on endothelial transportome diversity. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.