Over-expression of parathyroid hormone Type 1 receptor confers an aggressive phenotype in osteosarcoma Academic Article uri icon

Overview

MeSH Major

  • Osteosarcoma
  • Receptor, Parathyroid Hormone, Type 1

abstract

  • Osteosarcoma is the most common primary bone malignancy in children and is associated with rapid bone growth. Parathyroid hormone-related peptide (PTHrP) signaling via parathyroid hormone Type 1 receptor (PTHR1) is important for skeletal development and is involved in bone metastases in other tumors. The aim of this study was to investigate the status of PTHrP/PTHR1 and its possible role in osteosarcoma. In a preliminary screening, a higher level of PTHR1 mRNA, but not PTHrP, was found in 4 osteosarcoma xenografts as compared with 4 standard cell lines, or 5 patient derived cell lines (p < 0.05) using quantitative RT-PCR. It was therefore extended to 55 patient specimens, in which a significantly higher level of PTHR1 mRNA was detected in metastatic or relapsed samples than those from primary sites (p < 0.01). Cell behavior caused by PTHR1 overexpression was further studied in vitro using PTHR1 transfected HOS cell line as a model. Over-expression of PHTR1 resulted in increased proliferation, motility and Matrigel invasion without addition of exogenous PTHrP suggesting an autocrine effect. Importantly, the aggressiveness in PTHR1-expressing cells was completely reversed by RNAi mediated gene knockdown. In addition, PTHR1 over-expression led to delayed osteoblastic differentiation and upregulation of genes involved in extracellular matrix production, such as TGF-beta1 and connective tissue growth factor. When cocultured with bone marrow derived monocytes, PTHR1 transfected HOS cells induced a greater number of osteoclasts. This study suggests that PTHR1 over-expression may promote osteosarcoma progression by conferring a more aggressive phenotype, and forming a more favorable microenvironment.

publication date

  • September 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1002/ijc.22749

PubMed ID

  • 17410535

Additional Document Info

start page

  • 943

end page

  • 54

volume

  • 121

number

  • 5