| Project/Area Number |
23689023
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
ITOH Fumiko 東京薬科大学, 生命科学部, 准教授 (70502582)
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| Project Period (FY) |
2011-11-18 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2013: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | TGF-β / 血管新生 / リンパ管新生 / 腫瘍 / 転移 / 遺伝子改変マウス / がん転移 / タモキシフェン / リンパ管 / 腫瘍血管新生 / 腫瘍リンパ管新生 / 低酸素 / E2-2 / FAM96B |
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| Research Abstract |
It is not clear how TGF-b signaling affects vascular formation in postnatal mice. To address this issue, TGF-b type II receptor conditional knockout (CKO) mice; TbRIIF/F, were crossed with Pdgfb-icreER and Prox1-CreERT2 mice in which Cre recombinase is induced in blood (BECs) and lymphatic vascular endothelial cells (LECs) by tamoxifen (Tx), respectively.
When LLC cells were subcutaneously injected into TbRIIF/F; Pdgfb-icreER (TbRIIBEC-CKO), TbRII;Prox1-CreERT2 (bRIILEC-CKO) mice , both tumor and lymphangiogenesis were enhanced in CKO mice. Moreover, lung metastasis was decreased when B16 melanoma cells were injected into foot pad in both CKO mice. Blood vessels in the tumor but not in the normal tissue of TbRIIBEC-CKO mice were very leaky, indicating the poor blood circulation in tumors. Furthermore, deletion of TGF-b signaling in LEC resulted in the reduced drainage and edema. These results indicated that TGF-b signaling inhibits tumor angiogenesis and lymphangiogenesis in adults.
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