2013 Fiscal Year Final Research Report
The role of TGF-b signaling in blood and lymph angiogenesis
| 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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| 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 |
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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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[Journal Article] C18ORF1: A Novel Negative Regulator of TGF-βSignaling2012
Author(s)
Nakano, N., Maeyama, K., Ikeno, S., Itoh, F., Togawa, Y., Katsu, Y., Thanh Thao, V.N., Watanabe, Y., Kato, M., and Itoh, S
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Journal Title
J. Biol. Chem
Volume: 289
Pages: 12680-12692
DOI
Peer Reviewed
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[Presentation] The role of TGF-βsignaling in Tumor blood- and lymph angiogenesis2013
Author(s)
Itoh, F., Takagi, T., Ichikawa, K., Fruttiger, M., Oliver, G., Itoh S., and Watanabe, T
Organizer
The 3^<rd> International Symposium by JSPS Core-to-Core Program"Cooperative International Frame work in TGF-βFamily Signaling"
Place of Presentation
Matsuyama, Japan
Year and Date
20131000
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[Presentation] TGF-βsignaling controls tumor blood- and lymph- angiogenesis. FASEB Summer Research conference2013
Author(s)
Itoh, F., Takagi, T., Ichikawa, K., Fruttiger, M, Oliver, G., Watanabe, T., and Itoh, S
Organizer
TGF-βsuperfamily : Signaling in Development and Disease
Place of Presentation
Steamboat springs, Colorado, USA
Year and Date
20130800
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[Presentation] Dicer-dependent miRNA pathway is important for vascular development2012
Author(s)
Itoh, F., Hazome, S., Fruttiger, M., Itoh, S., and Watanabe, T
Organizer
10th Korea-Japan Joint Symposium on Vasuclar Biology
Place of Presentation
Tokushima, Japan
Year and Date
20121200
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