Title:Inorganic Phosphate (Pi) in the Breast Cancer Microenvironment: Production,
Transport and Signal Transduction as Potential Targets for Anticancer
Strategies
Volume: 23
Issue: 3
关键词:
无机磷酸盐，乳腺癌微环境，外核苷酶，外磷酸酶，H+依赖的Pi转运，Na+依赖的Pi转运。
摘要: Tumor cells develop a high demand for inorganic phosphate (Pi) due to their high growth
rates and energy requirements. Serum Pi concentrations in cancer patients have been found to be two
to four times higher than baseline levels in healthy individuals. Twofold Pi accumulation was observed
in breast cancer cells in the mouse tumor microenvironment. In the breast tumoral microenvironment,
ectonucleotidases and ectophosphatases—presenting catalytic sites facing the extracellular
environment—could be involved in the extracellular release of Pi to be internalized by Pi transporters
to fuel the high energy requirement typical of cancer cells. Two Pi transporters were characterized in
breast cancer cells (Na+-dependent and H+-dependent) with strong associations with tumor processes
such as proliferation, migration, adhesion, and epithelium-mesenchymal transition (EMT). Moreover,
a high extracellular Pi concentration stimulates ROS production in triple-negative breast cancer cells
by Pi transport stimulation. Several compounds show a potent ability to inhibit ectonucleotidases, ectophosphatases,
Pi transporters, and Pi-modulated signal pathways in breast cancer cells and regulate
proliferation, migration, adhesion, and EMT. This review article aimed to gather the relevant experimental
records regarding Pi's effects on the breast cancer microenvironment and points to possible inhibitors
for ectonucleotidases, ectophosphatases, Pi transporters, and Pi-modulated signal pathways as
potential chemotherapeutic agents or Pi acting as a potent enhancer of classical chemical-induced cytotoxicity
in triple-negative breast cancer cells.
