| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
The aim of this study is to clarify the role of tumor-derived exosome in their microenvironment using multiple myeloma cell lines which show continuous growth in vitro under chronically hypoxic conditions (hypoxia-resistant MM cells; HR-MM cells). We isolated the exosomes from HR-MM cells and assessed exosomal miRNA profiling using the TaqMan low-density array. Endothelial tube formation assay was used for validating function of MM cell-endothelial cell (HUVECs) communication. We found miR-135b was significantly up-regulated in exosomes from HR-MM cells compared to those in the parental cells. The exosomal miR-135b directly suppressed its target, factor inhibiting HIF-1 (FIH-1), in endothelial cells, and enhanced endothelial tube formation under hypoxia. HR-MM cell-derived exosomes could enhance density of CD31 positive endothelial cells in Matrigel plug. Suggesting that the exosomal miR-135b might therefore be one of promising target for controlling angiogenesis in MM.
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