Direct anti-metastatic efficacy by the DNA enzyme Dz13 and downregulated MMP-2, MMP-9 and MT1-MMP in tumours
1 Department of Orthopaedics, St Vincent's Hospital Melbourne, Fitzroy, VIC 3065, Australia
2 Department of Medicine, University of Melbourne, Parkville, VIC 3010, Australia
3 Department of Surgery, University of Melbourne, Parkville, VIC 3010, Australia
4 Sarcoma Service, Peter MacCallum Cancer Institute, East Melbourne, VIC 3002, Australia
Cancer Cell International 2010, 10:9 doi:10.1186/1475-2867-10-9Published: 24 March 2010
The DNA enzyme Dz13, targeted against the oncogene c-Jun, is capable of inhibiting various model tumours in mice albeit in ectopic models of neoplasia. In previous studies using orthotopic models of disease, the inhibitory effects of Dz13 on secondary growth was a direct result of growth inhibition at the primary lesion site. Thus, the direct and genuine effects on metastasis were not gauged. In this study, Dz13 was able to inhibit both locoregional and distal metastasis of tumour cells in mice, in studies where the primary tumours were unaffected due to the late and clinically-mimicking nature of treatment commencement. In addition, the effect of Dz13 against tumours has now been extended to encompass breast and prostate cancer. Dz13 upregulated the matrix metalloproteinase (MMP)-2 and MMP-9, and decreased expression of MT1-MMP (MMP-14) in cultured tumour cells. However, in sections of ectopic tumours treated with Dz13, both MMP-2 and MMP-9 were downregulated. Thus, not only is Dz13 able to inhibit tumour growth at the primary site, but also able to decrease the ability of neoplastic cells to metastasise. These findings further highlight the growing potential of Dz13 as an antineoplastic agent.