Osteosarcoma (OS) is the most common malignant primary bone tumour in humans and dogs. Several studies have established the vital role of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation and remodeling. In addition, these molecules play a role in the progression and metastasis of many human tumour types. This study investigated the expression of PTHR1 and PTHrP in canine OS tissues and assessed their prognostic value. Formalin-fixed, paraffin-embedded tissue samples from 50 dogs diagnosed with primary OS were immunolabeled with antibodies specific for PTHR1 and PTHrP. The immunostaining intensity of tumours from patients with OS was correlated with survival time. Both PTHR1 and PTHrP were detected in all OS samples (n = 50). Dogs with OS tumours showing high immunostaining intensity for PTHR1 (n = 36) had significantly shorter survival times (p = 0.028, Log Rank; p = 0.04, Cox regression) when compared with OS that had low immunostaining intensity for PTHR1 (n = 14).PTHrP immunostaining intensity did not correlate with survival time (p > 0.05). The results of this study indicate that increased expression of PTHR1 antigen in canine OS is associated with poor prognosis. This suggests that PTHR1 may be useful as a prognostic indicator in canine oS.Osteosarcoma (OS) is a malignancy that originates from bone-forming mesenchymal cells 1 . It is the most prevalent type of primary bone cancer in both humans and dogs 2-5 . Canine OS represents 85-98% of all canine primary bone cancers and occurs more commonly in appendicular skeleton (75%) 6 . In the USA, more than 10,000 cases of canine OS are reported every year 7 .In the last 35 years, there has been little improvement in the treatment of human OS or its prognosis after treatment with surgery and chemotherapy, especially for patients with metastatic OS 8 . It has been found that the median survival times of dogs suffering from OS and receiving standard care (surgery and adjuvant chemotherapy) is from three months to one year and that less than 20% will be alive more than two years after diagnosis 9 . So, there is a need to identify indicators for early diagnosis and prediction of prognosis in OS which may assist in improvement of patient survival.Parathyroid hormone-related protein (PTHrP) was discovered as the factor responsible for causing hypercalcemia of malignancy in some tumours 10 . Parathyroid hormone (PTH) and PTHrP share a similar amino acid sequence in the N-terminal region 10 . That allows the two to activate a common G-protein coupled receptor known as PTH/PTHrP receptor (PTHR1) 11 . PTHrP and its receptor are highly conserved amongst all vertebrates 12 .PTHrP is produced in many normal tissues where it acts as an autocrine/paracrine regulator of cell growth, development and differentiation 13 . In addition, PTHrP has been localised in numerous human cancers including breast cancers 14 , neuroendocrine cancers 15 , prostate cancers 16 , squamous cell carcinoma of skin 17 , pancreatic adenocarcinoma 18 , intrahepatic ch...
Osteosarcoma (OS) is the most common primary bone tumor and originates from bone forming mesenchymal cells and primarily affects children and adolescents. The 5-year survival rate for OS is 60 to 65%, with little improvement in prognosis during the last four decades. Studies have demonstrated the evolving roles of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation, bone remodeling, regulation of calcium transport from blood to milk, regulation of maternal calcium transport to the fetus and reabsorption of calcium in kidneys. These two molecules also play critical roles in the development, progression and metastasis of several tumors such as breast cancer, lung carcinoma, chondrosarcoma, squamous cell carcinoma, melanoma and OS. The protein expression of both PTHrP and PTHR1 have been demonstrated in OS, and their functions and proposed signaling pathways have been investigated yet their roles in OS have not been fully elucidated. This review aims to discuss the latest research with PTHrP and PTHR1 in OS tumorigenesis and possible mechanistic pathways.This review is dedicated to Professor Michael Day who died in May 2020 and was a very generous collaborator.
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