Increased expression of insulin-like growth factor-1 receptor is correlated with tumor metastasis and prognosis in patients with osteosarcoma

J Surg Oncol. 2012 Mar;105(3):235-43. doi: 10.1002/jso.22077. Epub 2011 Aug 22.

Abstract

Background: The aim of this study was to investigate the association of insulin-like growth factor-1 receptor (IGF-1R) with metastasis and prognosis of osteosarcoma patients.

Methods: RT-PCR and Western blot assays were performed to detect IGF-1R mRNA and protein expression in 26 osteosarcoma and noncancerous bone tissues. Immunohistochemistry was performed to analyze the correlation of IGF-1R expression in 84 osteosarcoma tissues with clinicopathological factors or survival of patients. Lentivirus-mediated RNA interference system was employed to downregulate IGF-1R expression and analyze the effects of IGF-1R downregulation on invasion and metastasis of osteosarcoma cells.

Results: The relative levels of IGF-1R mRNA and protein expression were significantly higher in osteosarcoma tissues than in corresponding noncancerous bone tissues. The expression of IGF-1R protein was closely associated with surgical stage and distant metastasis of osteosarcoma patients. Osteosarcoma patients with high IGF-1R expression had poorer survival, and multivariate Cox analyses showed that high IGF-1R expression was an independent prognostic maker. Lentivirus-mediated targeting IGF-1R could significantly inhibit adhesion, migration, invasion, and metastasis of osteosarcoma cells, which might be correlated with of inactivation of Akt signaling pathway.

Conclusions: IGF-1R is an independent prognostic marker for osteosarcoma patients and increased expression of this molecular is correlated with metastasis of osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / mortality*
  • Bone Neoplasms / pathology*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation
  • Female
  • Genetic Vectors
  • Humans
  • Immunohistochemistry
  • Lentivirus / genetics
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Osteosarcoma / metabolism
  • Osteosarcoma / mortality*
  • Osteosarcoma / pathology*
  • Prognosis
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transduction, Genetic

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptor, IGF Type 1
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9