PTHR1 in osteosarcoma: Specific molecular mechanisms and comprehensive functional perspective

Abstract

Osteosarcoma occurs largely in children and adolescents and is the most common primary malignant tumour of bone. Although surgical advances and neoadjuvant chemotherapy have made great strides in recent years, rates of local recurrence and lung metastasis remain high, with a plateau in overall survival during the past decade. It is thus urgent to explore the pathogenesis of osteosarcoma and identify potential therapeutic targets. Parathyroid hormone receptor 1 (PTHR1) belongs to the broad family of G protein–coupled receptors, binding both parathyroid hormone (PTH) and parathyroid hormone–related peptide (PTHrP, a paracrine factor). Previous studies have shown that in tissues and cells of osteosarcoma, expression of PTHR1 is markedly increased, correlating with aggressive biologic behaviour and a poor prognosis. PTHR1 expression also correlates closely with epigenetic regulation, transcriptional regulation, post-translational modification and protein interaction. Herein, we have summarized the latest research on the role played by PTHR1 in progression of osteosarcoma, assessing its clinical utility as a novel biomarker and its therapeutic ramifications.