H+-dependent inorganic phosphate transporter in breast cancer cells: Possible functions in the tumor microenvironment

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2019-09, Vol.1865 (9), p.2180-2188
• Main Authors: Lacerda-Abreu, Marco Antonio, Russo-Abrahão, Thais, Cosentino-Gomes, Daniela, Nascimento, Michelle Tanny Cunha, Carvalho-Kelly, Luiz Fernando, Gomes, Tainá, Rodrigues, Mariana Figueiredo, König, Sandra, Rumjanek, Franklin David, Monteiro, Robson Q., Meyer-Fernandes, José Roberto
• Format: Article
• Language: English
• Subjects: Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cadherins - genetics; Cadherins - metabolism; Cell Adhesion; Cell Line; Cell Proliferation; Down-Regulation - drug effects; Female; H+-dependent Pi transport; Humans; Hydrogen-Ion Concentration; Inorganic phosphate; Ion Transport - drug effects; Kinetics; MDA-MB-231; Phosphate Transport Proteins - metabolism; Phosphates - metabolism; Phosphonoacetic Acid - pharmacology; Sodium-Phosphate Cotransporter Proteins, Type IIb - genetics; Sodium-Phosphate Cotransporter Proteins, Type IIb - metabolism; Tumor Microenvironment; Up-Regulation - drug effects
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2019.04.015

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. •MDA-MB-231 presented higher H+-dependent Pi transport than MCF-10A.•PAA, an inorganic phosphate analogue, inhibited H+-dependent Pi transport.•High extracellular Pi concentration stimulated H+-dependent Pi transport.