Explore the factors for overcoming cancer metastasis

Japanese

Laboratory of Cancer metastasis

Summary of research:

The aim and object of our study is to develop clinically applicable strategies to predict and inhibit metastasis by analyses of factors that confer metastatic ability to tumor cells.
Recently, we found that ROS (reactive oxygen species)-generating pathogenic mitochondrial DNA (mtDNA) mutations enhance metastatic ability of Lewis lung carcinoma cells and mouse fibrosarcoma cells by increasing the expression of hypoxia-inducible factor-1α (HIF-1α) and antiapoptotic Mcl-1. Furthermore, we found that antioxidants can inhibit metastasis caused by such mtDNA mutations.
We are now trying to reveal the relationship between pathogenic mtDNA mutations and metastasis in human tumor cell lines, and also in clinical samples by carrying out prospective and perspective studies, aiming to apply the outcome of the analyses for clinical use in the future.

Keywords:

Metastasis, Mitochondria, Tumor micro-environment, Reactive oxygen species, Hypoxia

Recent main publications:

• Ishikawa K et al. Science 2008：661-664
• Ishikawa K et al. FEBS Lett. 2008：3525-3530
• Ito S et al. Int. J Oncol. 2007：261-268
• Ito A et al. Biochem Biophys Res Commun. 2006：306-311
• Koshikawa N et al. Oncogene 2006：917-928