ArticleOncogene2015
Knockdown of PTHR1 in osteosarcoma cells decreases invasion and growth and increases tumor differentiation in vivo.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Decreased expression of PTH1R is a poor prognosis in hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2018Pooled it
- Genetics and Molecular Mechanisms in Oral Squamous Cell Carcinoma: A Narrative Review.Medicina (Kaunas, Lithuania) · 2026Review
- Advances in targeted therapies for pediatric tumors.Acta pharmacologica Sinica · 2026Article
- Conventional osteosarcoma of the ilium masquerading as a brown tumor in primary hyperparathyroidism: a rare case report and literature review.Frontiers in oncology · 2026Article
- Parathyroid Hormone-Related Protein/Parathyroid Hormone Receptor 1 Signaling in Cancer and Metastasis.Cancers · 2023Review
- Parathyroid hormone 1 receptor signaling mediates breast cancer metastasis to bone in mice.JCI insight · 2023Article
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- PTHR1 in osteosarcoma: Specific molecular mechanisms and comprehensive functional perspective.Journal of cellular and molecular medicine · 2021Review
- Parathyroid hormone type 1 receptor regulates osteosarcoma K7M2 Cell growth by interacting with angiotensinogen.Journal of cellular and molecular medicine · 2021Article
- Roles of Parathyroid Hormone-Related Protein (PTHrP) and Its Receptor (PTHR1) in Normal and Tumor Tissues: Focus on Their Roles in Osteosarcoma.Frontiers in veterinary science · 2021Review
- Identification of Hub Genes Associated With Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis.Frontiers in oncology · 2021Article
- Mangiferin suppresses human metastatic osteosarcoma cell growth by down-regulating the expression of metalloproteinases-1/2 and parathyroid hormone receptor 1.AMB Express · 2020Article
- Osteosarcoma in the Post Genome Era: Preclinical Models and Approaches to Identify Tractable Therapeutic Targets.Current osteoporosis reports · 2019Review
- Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice.BMC cancer · 2019Article
- Parathyroid hormone-like hormone plays a dual role in neuroblastoma depending on PTH1R expression.Molecular oncology · 2019Article
- Molecular and cellular mechanisms for zoledronic acid-loaded magnesium-strontium alloys to inhibit giant cell tumors of bone.Acta biomaterialia · 2018Article
- Small animal models for the study of bone sarcoma pathogenesis:characteristics, therapeutic interests and limitations.Journal of bone oncology · 2018Review
- Tolerance to sustained activation of the cAMP/Creb pathway activity in osteoblastic cells is enabled by loss of p53.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) is the most common cancer of bone. Parathyroid hormone (PTH) regulates calcium homeostasis and bone development, while the paracrine/autocrine PTH-related protein (PTHrP) has central roles in endochondral bone formation and bone remodeling. Using a murine OS model, we found that OS cells express PTHrP and the common PTH/PTHrP receptor (PTHR1). To investigate the role of PTHR1 signaling in OS cell behavior, we used shRNA to reduce PTHR1 expression. This only mildly inhibited proliferation in vitro, but markedly reduced invasion through collagen and reduced expression of RANK ligand (RANKL). Administration of PTH(1-34) did not stimulate OS proliferation in vivo but, strikingly, PTHR1 knockdown resulted in a profound growth inhibition and increased differentiation/mineralization of the tumors. Treatment with neutralizing antibody to PTHrP did not recapitulate the knockdown of PTHR1. Consistent with this lack of activity, PTHrP was predominantly intracellular in OS cells. Knockdown of PTHR1 resulted in increased expression of late osteoblast differentiation genes and upregulation of Wnt antagonists. RANKL production was reduced in knockdown tumors, providing for reduced homotypic signaling through the receptor, RANK. Loss of PTHR1 resulted in the coordinated loss of gene signatures associated with the polycomb repressive complex 2 (PRC2). Using Ezh2 inhibitors, we demonstrate that the increased expression of osteoblast maturation markers is in part mediated by the loss of PRC2 activity. Collectively these results demonstrate that PTHR1 signaling is important in maintaining OS proliferation and undifferentiated state. This is in part mediated by intracellular PTHrP and through regulation of the OS epigenome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.