title: Ovarian cancer: Ion channel and aquaporin expression as novel targets of clinical potential.
abstract: Ovarian cancer is associated with limited overall survival, due to problems in early detection and therapy. Membrane ion channels have been proposed to play a significant, concerted role in the cancer process, from initial proliferation to metastasis, and promise to be early, functional biomarkers. We review the evidence for ion channel and aquaporin expression and functioning in human ovarian cancer cells and tissues. In vitro, K(+) channels, mainly voltage-gated, including Ca(2+)-activated channels, have been found to control the cell cycle, as in other cancers. Voltage-gated, volume-regulated and intracellular Cl(-) channels have been detected in vitro and in vivo and shown to be involved in proliferation, adhesion and invasion. Evidence for 'transient receptor potential', voltage-gated sodium and calcium channels, which have been shown to contribute to pathogenesis of other carcinomas, is also emerging in ovarian cancer. Aquaporins may be involved in cell growth, migration and formation of ascites via increased water permeability of micro-vessels. It is concluded that functional expression of ion channels and their regulation by steroid hormones and growth factors are an integral part of ovarian cancer development and progression. Furthermore, ion channels may be involved in multidrug resistance, commonly associated with treatment of ovarian cancer. We propose that ion channel studies can facilitate our understanding of the pathobiology of ovarian cancer and, ultimately, can serve as viable novel targets for its clinical management.
authors.affiliation: Division of Cell and Molecular Biology, Neuroscience Solutions to Cancer Research Group, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Frede
authors.forename: Scott P
authors.initials: SP
authors.lastname: Fraser
authors.forename: Gülten
authors.initials: G
authors.lastname: Oskay-Özcelik
authors.forename: Yeosun
authors.initials: Y
authors.lastname: Hong
authors.forename: E
authors.initials: E
authors.lastname: Ioana Braicu
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
authors.forename: Mustafa B A
authors.initials: MB
authors.lastname: Djamgoz
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D020346:Aquaporins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D020346:Aquaporins; D007473:Ion Channels