title: Vacuolar H+-ATPase in human breast cancer cells with distinct metastatic potential: distribution and functional activity.
abstract: Tumor cells thrive in a hypoxic microenvironment with an acidic extracellular pH. To survive in this harsh environment, tumor cells must exhibit a dynamic cytosolic pH regulatory system. We hypothesize that vacuolar H(+)-ATPases (V-ATPases) that normally reside in acidic organelles are also located at the cell surface, thus regulating cytosolic pH and exacerbating the migratory ability of metastatic cells. Immunocytochemical data revealed for the first time that V-ATPase is located at the plasma membrane of human breast cancer cells: prominent in the highly metastatic and inconspicuous in the lowly metastatic cells. The V-ATPase activities in isolated plasma membranes were greater in highly than in lowly metastatic cells. The proton fluxes via V-ATPase evaluated by fluorescence spectroscopy in living cells were greater in highly than in lowly metastatic cells. Interestingly, lowly metastatic cells preferentially used the ubiquitous Na(+)/H(+) exchanger and HCO(3)(-)-based H(+)-transporting mechanisms, whereas highly metastatic cells used plasma membrane V-ATPases. The highly metastatic cells were more invasive and migratory than the lowly metastatic cells. V-ATPase inhibitors decreased the invasion and migration in the highly metastatic cells. Altogether, these data indicate that V-ATPases located at the plasma membrane are involved in the acquisition of a more metastatic phenotype.
authors.affiliation: Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430-6551, USA. souad.sennoune@ttuhsc.edu
authors.forename: Souad R
authors.initials: SR
authors.lastname: Sennoune
authors.forename: Karina
authors.initials: K
authors.lastname: Bakunts
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Martínez
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Chua-Tuan
authors.forename: Yamina
authors.initials: Y
authors.lastname: Kebir
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Attaya
authors.forename: Raul
authors.initials: R
authors.lastname: Martínez-Zaguilán
mesh_terms: D000136:Acid-Base Equilibrium / Q000502:physiology; D001639:Bicarbonates / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000503:physiopathology*; D002277:Carcinoma / Q000201:enzymology* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D010641:Phenotype; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D004791:Enzyme Inhibitors; D017923:Sodium-Hydrogen Exchangers; D025262:Vacuolar Proton-Translocating ATPases