INORGANIC PHOSPHATE AS A NOVEL SIGNALING MOLECULE: ITS POTENTIAL USE IN THE OSTEOSARCOMA THERAPY

There is a pressing need for the development of new and alternative approaches to the treatment of osteosarcoma. In this regard, naturally occurring molecules with antitumor activity and with the least toxicity to normal tissues are suggested as possible candidates to be investigated for their synergistic efficacy in combination with anticancer drugs. Inorganic phosphate (Pi) is an essential nutrient to the living organisms. It is required as a component of energy metabolism, kinase/phosphatase signaling and in the formation and function of lipids, carbohydrates and nucleic acids and, at systemic level, it plays a key role for the normal skeletal and dentin mineralization. Pi represents an abundant dietary element and its intestinal absorption is efficient and minimally regulated. The kidney is a major regulator of the Pi homeostasis and can increase or decrease its Pi reabsorptive capacity to accommodate the Pi need. Relevantly, Pi is emerging as an important signaling molecule capable of modulating multiple cellular functions by altering signal transduction pathways, gene expression and protein abundance in many cell types. Recently, a series of articles directed at determining the consequences of elevated Pi on the behaviour of human osteosarcoma cells has been published. Overall, evidence has been accumulating that enhances the proposal of Pi as a signaling molecule and indicates that Pi may act as a potent antitumor agent in osteosarcoma cells. The main results, the underlying molecular mechanisms, the potential clinical significance and therapeutic applications by these studies will be presented.