Downregulation of uPAR confirms link in growth and metastasis of osteosarcoma

Full text for this resource is not available from the Research Repository.

Dass, Crispin R, Nadesapillai, Anne P. W, Robin, Daniel, Howard, Monique L, Fisher, Jane L, 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

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.

Dimensions Badge

Altmetric Badge

Item type Article
URI https://vuir.vu.edu.au/id/eprint/7595
DOI https://doi.org/10.1007/s10585-006-9004-3
Official URL http://dx.doi.org/10.1007/s10585-006-9004-3
Subjects Historical > Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
Historical > FOR Classification > 1112 Oncology and Carcinogenesis
Historical > SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Keywords ResPubID21893. uPAR, uPA, antisense, cancer, metastasis, osteosarcoma, urokinase plasminogen activator
Citations in Scopus 45 - View on Scopus
Download/View statistics View download statistics for this item

Search Google Scholar

Repository staff login