Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Outline of Final Research Achievements |
We set the hypothesis that cancer cells arrived at the bone microenvironment (bone ME), would survive with phenotype similar to cancer stem cells. We found that miR205 was down-regulated in the bone ME. miR205 overexpressing tumor cell lines (miR205+cells) were established and involvement of EMT was found. We also found that the drug sensitivity of inhibitors of ER, AR and HER2 were enhanced in miR205+cells. IHC study of SOX2, one of the cancer stem cell marker, revealed that SOX2+ cells were observed in the bone ME and that the number of SOX2+ cells was significantly lower than that of control after trasplant of miR205+ cells. Cathepsin D was regulated by miR205 in the tumor cells and whosehigh expression were correlated with clinical stage and T grade of TNM classification. Taken together, miR205 may be involved in the survival, induction of EMT, and drug resistance of the tumor cells in the bone ME, all of which are malignant phenotypes of clinically defined bone metastasis.
|