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Downregulation of uPAR confirms link in growth and metastasis of osteosarcoma

Dass, Crispin R and Nadesapillai, Anne P. W and Robin, Daniel and Howard, Monique L and Fisher, Jane L and Zhou, Hong and Choong, Peter F. M (2005) Downregulation of uPAR confirms link in growth and metastasis of osteosarcoma. Clinical and Experimental Metastasis, 22 (8). pp. 643-652. ISSN 0262-0898

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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.

Item Type: Article
Uncontrolled Keywords: ResPubID21893. uPAR, uPA, antisense, cancer, metastasis, osteosarcoma, urokinase plasminogen activator
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 1112 Oncology and Carcinogenesis
SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Depositing User: VUIR
Date Deposited: 21 Oct 2011 00:32
Last Modified: 03 Feb 2015 00:22
URI: http://vuir.vu.edu.au/id/eprint/7595
DOI: 10.1007/s10585-006-9004-3
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Citations in Scopus: 35 - View on Scopus

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