The role of P2X7R purinoreceptor in osteosarcoma

This is the authors' abstract. We don't add key points for this paper.

Osteosarcoma is the most common type of bone cancer, which appears mainly in the metaphysis of long bones, especially in males between the age of 0–14 years. Malignancy usually emerges with the abnormal growth of tumor-forming bone cells. These tumor cells act like new bones that are responsible for the spread of sarcoma throughout the bone matrix. In this review, we focused on the expression and function of the P2X7 receptor (P2X7R) as a therapeutic target in osteosarcoma malignancy. Two known human P2X7R functional splice variants in osteosarcoma cell growth are the full length P2X7RA and the truncated P2X7RB. The stimulation of growth is attributed to an increase (i) in the mobilization of Ca²⁺ ions, and (ii) in the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) activity. Furthermore, Te85 P2X7RA+B cells caused membrane depolarization and spontaneous release of extracellular adenosine triphosphate (ATP). The P2X7R agonist, benzoyl adenosine triphosphate (BzATP), may increase the liberation of ATP and this may be regulated by P2X7R. As a result, cell proliferation occurs with the spread of osteosarcoma throughout the bone matrix. BzATP also increases cell growth and activates NFATc1 to make it cancerous. In this review, we have highlighted the crucial role of the P2X7R purinoreceptor in osteosarcoma pathogenesis. It is an upstream regulator of all paths that may inhibit the receptor activator of nuclear factor kappa-B ligand (RANKL) and a mechanistic target of rapamycin (mTOR) blockers. This review suggests that P2X7R is an attractive therapeutic target for osteosarcoma.