Downregulation of uPAR confirms link in growth and metastasis of osteosarcoma.

Clinical & Experimental Metastasis
Crispin R DassPeter F M Choong

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 obser...Continue Reading

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Citations

Oct 13, 2006·Journal of Cancer Research and Clinical Oncology·Crispin R DassPeter F M Choong
Aug 11, 2007·DNA and Cell Biology·Crispin R Dass, Peter F Choong
May 4, 2011·Vascular Cell·Rashna D BalsaraVictoria A Ploplis
Aug 24, 2011·Clinical Chemistry and Laboratory Medicine : CCLM·Evi DebruyneJoris Delanghe
Jun 6, 2013·Biomarkers in Medicine·Helge TaubertMatthias Kotzsch
Oct 30, 2007·Journal of Cancer Research and Clinical Oncology·Jonathan C M ClarkPeter F M Choong
Nov 20, 2009·Expert Opinion on Therapeutic Targets·Matthew L BroadheadPeter F M Choong
Dec 7, 2013·Expert Review of Anticancer Therapy·Nataraj Vijayamurugan, Sameer Bakhshi
Apr 20, 2010·Expert Review of Anticancer Therapy·Matthew L BroadheadCrispin R Dass
Jan 1, 2009·Expert Opinion on Medical Diagnostics·Colin Kong, Marc F Hansen
Apr 25, 2007·Journal of Drug Targeting·Crispin R Dass, Peter F M Choong
May 12, 2011·Sarcoma·Matthew L BroadheadPeter F M Choong
Nov 7, 2006·Trends in Biotechnology·Vinochani PillayPeter F M Choong
Jun 3, 2009·Cancer Science·Kazuhito MoriokaKoichi Matsuda
Apr 3, 2008·The Journal of Pharmacy and Pharmacology·Crispin R Dass, Peter F M Choong
Oct 26, 2010·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jianda XuXin Shi
Sep 12, 2014·The Journal of Pharmacy and Pharmacology·Oktay TacarCrispin R Dass
Dec 21, 2018·Expert Review of Clinical Immunology·Concetta SchianoClaudio Napoli
Feb 14, 2009·Cancer Metastasis Reviews·Hang T TaDave E Dunstan
Nov 13, 2013·Cancers·Atta GoudarziIrene L Andrulis

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