H+-dependent inorganic phosphate transporter in breast cancer cells: Possible functions in the tumor microenvironment |
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Authors: | Marco Antonio Lacerda-Abreu Thais Russo-Abrahão Daniela Cosentino-Gomes Michelle Tanny Cunha Nascimento Luiz Fernando Carvalho-Kelly Tainá Gomes Mariana Figueiredo Rodrigues Sandra König Franklin David Rumjanek Robson Q Monteiro José Roberto Meyer-Fernandes |
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Institution: | 1. Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, RJ, Brazil;2. Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro, RJ, Brazil;3. Instituto de Ciência Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brazil |
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Abstract: | Tumor microenvironment has a high concentration of inorganic phosphate (Pi), which is actually a marker for tumor progression. Regarding Pi another class of transporter has been recently studied, an H+-dependent Pi transporter, that is stimulated at acidic pH in Caco2BBE human intestinal cells. In this study, we characterized the H+-dependent Pi transport in breast cancer cell (MDA-MB-231) and around the cancer tissue. MDA-MB-231 cell line presented higher levels of H+-dependent Pi transport as compared to other breast cell lines, such as MCF-10A, MCF-7 and T47-D. The Pi transport was linear as a function of time and exhibited a Michaelis-Menten kinetic of Km = 1.387 ± 0.1674 mM Pi and Vmax = 198.6 ± 10.23 Pi × h?1 × mg protein?1 hence reflecting a low affinity Pi transport. H+-dependent Pi uptake was higher at acidic pH. FCCP, Bafilomycin A1 and SCH28080, which deregulate the intracellular levels of protons, inhibited the H+-dependent Pi transport. No effect on pHi was observed in the absence of inorganic phosphate. PAA, an H+-dependent Pi transport inhibitor, reduced the Pi transport activity, cell proliferation, adhesion, and migration. Arsenate, a structural analog of Pi, inhibited the Pi transport. At high Pi conditions, the H+-dependent Pi transport was five-fold higher than the Na+-dependent Pi transport, thus reflecting a low affinity Pi transport. The occurrence of an H+-dependent Pi transporter in tumor cells may endow them with an alternative path for Pi uptake in situations in which Na+-dependent Pi transport is saturated within the tumor microenvironment, thus regulating the energetically expensive tumor processes. |
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Keywords: | Corresponding author at: Laboratório de Bioquímica Celular Instituto de Bioquímica Médica Leopoldo De Meis Universidade Federal do Rio de Janeiro CCS Cidade Universitária Rio de Janeiro RJ 21941-590 Brazil Inorganic phosphate + Breast cancer MDA-MB-231 |
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