Regulation of vascular homeostasis by AM-RAMP2 system and its therapeutic application for vascular abnormalities.
| Project/Area Number |
17K08588
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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, 医学部, 研究員 (50507506)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 血管 / 血管新生 / 転移 / 心血管、血液 |
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| Outline of Final Research Achievements |
We have reported that vasoactive peptide adrenomedullin (AM) and its receptor activity-modifying protein RAMP2 possess angiogenic function and regulate vascular homeostasis. On the other hand, AM and RAMP2 are highly expressed in various cancers. In this study, using drug-inducible endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2-/-), we analyzed the significance of AM-RAMP2 system in cancer angiogenesis and metastasis. In tumor implantation model, we found that angiogenesis of primary lesion was suppressed, whereas spontaneous lung metastasis was increased.
Vascular integrity regulated by the AM-RAMP2 system could thus be a hopeful therapeutic target for suppressing tumor metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
病的血管新生は、癌をはじめ、様々な疾患の発症や病態と深く関わっている。今回我々は、アドレノメデュリン(AM)-RAMP2 システムが、血管の恒常性維持に関わっている一方で、その破綻によって血管の恒常性が障害され、癌細胞が転移しやすい環境=転移前土壌が形成されることを見出した。AM-RAMP2系による血管恒常性維持作用に介入し、これを制御することは、従来の治療法とは異なり、癌腫を問わない治療法の開発につながる可能性がある。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Deficiency of the adrenomedullin-RAMP3 system suppresses metastasis through the modification of cancer-associated fibroblasts2020
Author(s)
Dai K, Tanaka M, Kamiyoshi A, Sakurai T, Ichikawa-Shindo Y, Kawate H, Cui N, Wei Y, Tanaka M, Kakihara S, Matsui S, Shindo T
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Journal Title
Oncogene
Volume: 39(9)
Issue: 9
Pages: 1914-1930
DOI
Related Report
Peer Reviewed
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[Journal Article] Endogenous Calcitonin Gene-Related Peptide Deficiency Exacerbates Postoperative Lymphedema by Suppressing Lymphatic Capillary Formation and M2 Macrophage Accumulation2019
Author(s)
Matsui S, Tanaka M, Kamiyoshi A, Sakurai T, Ichikawa-Shindo Y, Kawate H, Dai K, Cui N, Wei Y, Tanaka M, Kakihara S, Nakamura K, Yamauchi A, Ishida K, Tanaka S, Kawamata M, Shindo T
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Journal Title
Am J Pathol
Volume: 189(12)
Issue: 12
Pages: 2487-2502
DOI
Related Report
Peer Reviewed
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[Journal Article] Development of a novel model of central retinal vascular occlusion and the therapeutic potential of the adrenomedullin-RAMP2 system.2019
Author(s)
Hirabayashi K, Tanaka M, Imai A, Toriyama Y, Iesato Y, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, Dai K, Cui N, Wei Y, Nakamura K, Iida S, Matsui S, Yamauchi A, Murata T, Shindo T.
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Journal Title
Am J Pathol.
Volume: 189
Pages: 449-466
DOI
Related Report
Peer Reviewed
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[Journal Article] Adrenomedullin Suppresses Vascular Endothelial Growth Factor-Induced Vascular Hyperpermeability and Inflammation in Retinopathy.2017
Author(s)
Imai A, Toriyama Y, Iesato Y, Hirabayasi K, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, Liu T, Xian X, Zhai L, Dai K, Tanimura K, Liu T, Cui N, Yamauchi A, Murata T, Shindo T
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Journal Title
American journal of Pathology
Volume: 187(5)
Issue: 5
Pages: 999-1015
DOI
Related Report
Peer Reviewed
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[Presentation] Pathophysiological significance of adrenomedullin-RAMP2 system in age-related macular degeneration2019
Author(s)
Tanaka M, Hirabayashi K, Iesato Y, Imai A, Toriyama Y, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Tanaka M, Yamauchi A, Murata T, Shindo T.
Organizer
The Association for Research in Vision and Ophthalmology (ARVO) 2019
Related Report
Int'l Joint Research
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[Presentation] Loss of adrenomedullin-RAMP3 system suppresses inter-organ metastasis by regulation of podoplanin (PDPN) expression in cancer-associated fibroblasts (CAFs)2019
Author(s)
Dai K, Tanaka M, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Kawate H, Cui N, Wei Y, Matsui S, Nakamura K, Kakihara S, Yamauchi A, Shindo T.
Organizer
第78回日本癌学会
Related Report
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