| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
At the late stage of tumorigenesis, cancer cells produce TGF-β which promotes tumor proliferation and metastasis. Although angiogenesis is important for the growth of cancer cells, it remains veiled how abundant TGF-β plays a role in tumor angiogenesis. Hence, we have generated tamoxifen-inducible knockout mice of TGF-β type II receptor； TβRIIfl/fl; Pdgfb-iCreER (TβRIIiECΔ). When Lewis lung carcinoma (LLC) cells were transplanted into TβRIIiECΔ mice, there was no difference in tumor weight compared to control mice. Tumors formed in TβRIIiECΔ mice had increased angiogenesis, but the blood vessels were fragile and leaky. As blood flow was not secured in tunors, hypoxia could be observed in the tumors from TβRIIiECΔ mouse. When cancer cells invading blood vessels were counted using FACS, we found that circulating tumor cells were increased in TβRIIiECΔ mice. These results suggest that the TGF-β signal in endothelial cells inhibits angiogenesis and metastasis.
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