| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Outline of Final Research Achievements |
It is not well understood how Tumor-derived extracellular vesicles (TEVs) are delivered and effect on stromal cells in a tumor microenvironment. We identified a novel function of macrophages in delivery and transmission of TEVs. TEV incorporated macrophages (TEV-MΦ) increased invasion and widely disseminated. Upon contact with host stromal cells including mesothelial cells (MC), fibroblasts and endothelial cells, TEV-MΦs released membrane blebs containing TEVs. Then, scattered blebs were incorporated in these stromal cells, which transferred tumor-derived proteins and RNAs. Macrophage mediated transfer of TEVs caused myofibroblastic change in the recipient cells. In TEV-MΦ injected mice stomach, TEVs were delivered by MΦs to MCs covering the stomach, and MCs entered the gastric wall to create a niche that favored invasion of gastric cancer cells. These findings suggest a novel function of TAMs that transfer TEVs to surrounding stromal cells and increase CAF-like cells.
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