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Clinical & Experimental Metastasis

, Volume 22, Issue 8, pp 643–652 | Cite as

Downregulation of uPAR confirms link in growth and metastasis of osteosarcoma

  • Crispin R. Dass
  • Anne P. W. Nadesapillai
  • Daniel Robin
  • Monique L. Howard
  • Jane L. Fisher
  • Hong Zhou
  • Peter F. M. Choong
Article

Abstract

The uPA/uPAR system is involved in tumour progression and metastasis of a variety of cancers. Previously, we have shown that increased expression of urokinase plasminogen activator (uPA) correlated with malignancy grade in certain sarcomas. A study looking at in vivo inhibition of this system has not been done to date for osteosarcoma. More recently, this laboratory developed a clinically relevant mouse model where intratibial injection of UMR106-01 cells resulted in the development of osteosarcoma and lung metastases. Expression of uPA and its receptor (uPAR) were localised to the invading front of the tumours. Pulmonary metastasis is a predominant feature of the disease and is the major cause of death in patients. In the present study, the effects of down-regulating uPAR were observed in vitro and in vivo. UMR106-01 cells were transfected with either antisense-uPAR or vector control plasmids. Two antisense clones, exhibiting uPAR downregulation, demonstrated decreased adhesion, migration and invasion in cell-based assays in vitro (P<0.05). Cellular proliferation was not affected by uPAR downregulation. In␣vivo, a marked reduction of 80% in tibial tumour volumes (P<0.05), and total inhibition of pulmonary metastases were observed in mice injected with the more potent of the antisense clones. This study proves seminally the usefulness of uPAR antisense in curbing the growth and spread of osteosarcoma.

Keywords

antisense cancer metastasis osteosarcoma urokinase plasminogen activator 

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Notes

Acknowledgements

This work was supported by the Anti-Cancer Council of Victoria, and the Australian Orthopaedic Association. The authors thank Dr. Joseline Ojaimi for her critical reading of the manuscript.

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Crispin R. Dass
    • 1
  • Anne P. W. Nadesapillai
    • 1
  • Daniel Robin
    • 1
  • Monique L. Howard
    • 1
  • Jane L. Fisher
    • 2
  • Hong Zhou
    • 3
  • Peter F. M. Choong
    • 1
    • 4
  1. 1.Department of OrthopaedicsThe University of Melbourne, St. Vincent’s Hospital MelbourneFitzroyAustralia
  2. 2.St. Vincent’s Institute of Medical ResearchFitzroyAustralia
  3. 3.Department of MedicineThe University of Melbourne, St. Vincent’s Hospital MelbourneFitzroyAustralia
  4. 4.Division of Surgical OncologyPeter MacCallum Cancer InstituteEast MelbourneAustralia

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