A novel approach for cancer treatment based on homeostatic regulation of vascular system
| Project/Area Number |
26460337
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Shinshu University |
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Principal Investigator |
SHINDO Yuka 信州大学, 医学系研究科, 研究員 (50507506)
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| Co-Investigator(Renkei-kenkyūsha) |
TANIGUCHI Shun'ichiro 信州大学, 医学部, 特任教授 (60117166)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 血管新生 |
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| Outline of Final Research Achievements |
In this study, we used inducible vascular endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2-/-) to clarify the contribution made by the endogenous RAMP2 to tumor angiogenesis and metastasis. Subcutaneously transplanted melanoma cells showed less angiogenesis in DI-E-RAMP2-/- than control mice. On the other hand, after transplantation of melanoma cells into hindlimb footpads, spontaneous metastasis to the lung was enhanced in DI-E-RAMP2-/-. Within the lungs of DI-E-RAMP2-/-, pulmonary endothelial cells were deformed, vascular permeability was enhanced, and inflammatory cells infiltrated the vessel walls and expressed the chemotactic factors S100A8/9 and SAA3, which attract tumor cells and mediate formation of a pre-metastatic niche.
These findings indicate that vascular RAMP2 deletion promotes formation of pre-metastatic niche in distant organs by destabilizing the vascular structure and inducing vascular inflammation.
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Adrenomedullin-RAMP2 system suppresses ER stress-induced tubule cell death and is involved in kidney protection2014
Author(s)
Uetake R, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Iesato Y, Yoshizawa T, Koyama T, Yang L, Toriyama Y, Yamauchi A, Igarashi K, Tanaka M, Kuwabara T, Mori K, Yanagita M, Mukoyama M, Shindo T
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Journal Title
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Adrenomedullin-RAMP2 system as a novel therapeutic target of tumor angiogenesis and metastasis2014
Author(s)
Megumu Tanaka, Takayuki Sakurai, Akiko Kamiyoshi, Hisaka Kawate, Yuka Ichikawa-Shindo, Akihiro Yamauchi, Kyoko Igarashi, Yuichi Toriyama, Akira Imai, Tian Liu, Xian Xian, Liuyu Zhai, Shinji Owa, Takayuki Shindo
Organizer
The Conference on Bioactive Peptides for Cell-Cell Communication 2014
Place of Presentation
京都、ホテルグランヴィア
Year and Date
2014-09-11
Related Report
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[Presentation] アドレノメデュリン-RAMP2システムは、血管恒常性を維持し、癌転移前土壌の形成を抑制する。2014
Author(s)
田中愛, 桜井敬之, 神吉昭子, 河手久香, 新藤優佳, 小山晃英, 山内啓弘, 五十嵐恭子, 鳥山佑一, 劉甜, 羨鮮, 今井章, 谷口俊一郎, 新藤隆行
Organizer
第32回内分泌代謝学サマーセミナー
Place of Presentation
山梨、富士レークホテル
Year and Date
2014-07-10 – 2014-07-12
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[Presentation] アドレノメデュリン-RAMP2系は、血管恒常性を維持し、「癌転移前土壌」の形成を抑制する2014
Author(s)
田中愛, 小山晃英, 桜井敬之, 神吉昭子, 河手久香, 新藤優佳, 植竹龍一, 山内啓弘, 五十嵐恭子, 鳥山佑一, 劉甜, 羨鮮, 今井章, 谷口俊一郎, 新藤隆行
Organizer
第35回日本炎症・再生医学会
Place of Presentation
沖縄、万国津梁館
Year and Date
2014-07-01 – 2014-07-04
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[Presentation] Pathophysiological roles of endogenous calcitonin gene-related peptide in mouse model of laser induced choroidal neovascularization.2014
Author(s)
Yuichi Toriyama, Yasuhiro Iesato, Akira Imai, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Ryuichi Uetake, Akihiro Yamauchi, Megumu Tanaka, Xian Xian, Liu Tian, Takayuki Shindo, Toshinori Murata
Organizer
Association for Research in Vision and Ophthalmology (ARVO) 2014
Place of Presentation
オーランド、アメリカ
Year and Date
2014-05-04 – 2014-05-08
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[Presentation] Adrenomedullin-RAMP2 system of vascular endothelial cells inhibits the formation of "Pre-metastatic niche"2014
Author(s)
Megumu Tanaka, Teruhide Koyama, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Ichikawa-Shindo, Hisaka Kawate, Ryuichi Uetake, Akihiro Yamauchi, Kyoko Igarashi, Yuichi Toriyama, Takayuki Shindo
Organizer
The 18th International Vascular Biology Meeting 2014
Place of Presentation
京都、みやこメッセ
Year and Date
2014-04-14 – 2014-04-17
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