• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2021 Fiscal Year Final Research Report

Elucidation of the Regulatory Mechanism of Cancer Metastasis by the Adrenomedullin-RAMP2, 3 System and Development of Its Application

Research Project

  • PDF
Project/Area Number 20K16299
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionShinshu University

Principal Investigator

tanaka megumu  信州大学, 医学部, 研究員 (90786401)

Project Period (FY) 2020-04-01 – 2022-03-31
Keywordsアドレノメデュリン / RAMP2 / リンパ節転移 / 高内皮細静脈 / 血管恒常性
Outline of Final Research Achievements

Adrenomedullin (AM) was identified as a vasodilating peptide. We have reported that knockout mice of AM and its receptor-modulating protein RAMP2 are embryonic lethal with vascular abnormalities. Therefore, we generated drug-inducible knockout mice of RAMP2 to clarify the pathophysiological roles of vascular endothelial AM-RAMP2 system in adult.
In this study, transplantation of Lewis lung carcinoma cells into hindlimb footpads resulted in that spontaneous metastasis to the lymph node being enhanced in DI-E-RAMP2-/-. High endothelial venules (HEV) are blood vessels especially adapted for lymphocyte trafficking found in lymph nodes. DI-E-RAMP2-/- showed deformity of HEV. Furthermore, DI-E-RAMP2-/- showed abnormal distribution of T cells and dendritic cells within the lymph nodes, which may suppress immune system and allow the metastasis.
These findings indicate that disruption of vascular endothelial homeostasis is a promoting factor of tumor metastasis.

Free Research Field

腫瘍医学

Academic Significance and Societal Importance of the Research Achievements

アドレノメデュリン(AM)は血管拡張ペプチドとして同定されたが、それ以外にも多彩な作用を有することが知られている。様々な病態において、血中AM濃度が上昇することから、AMの臨床応用が期待されている。しかし、AMの血中半減期は短く、慢性疾患における臨床応用には制限がある。我々はAMの受容体活性調節タンパクであるRAMPの研究を行っている。今までの検討から、AM-RAMP2系は血管発生だけでなく、血管恒常性維持に必須であり、それらの破綻が癌転移を促進させる結果を見出した。現在、RAMPに結合する低分子化合物のスクリーニングを進めており、RAMP2の選択的活性化による癌転移抑制薬の開発が期待される。

URL: 

Published: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi