Analysis of the mechanism for pre-metastatic niche formation in lung metastasis of breast cancer cells.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20847
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Yamaguchi University (2022); Juntendo University (2021)
• Principal Investigator: Tominaga Kana 山口大学, 大学院医学系研究科, 助教 (50779569)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 乳がん / 浸潤・転移 / DNAマイクロアレイ / 肺繊維芽細胞 / 間質 / がん関連繊維芽細胞 / 前転移ニッチ

Outline of Final Research Achievements

To reveal the mechanism for the formation of metastasis between cancer cells and niche cells, we focused on pulmonary fibroblasts which involved in the formation of the pre-metastasis niche in breast cancer. First, we identified the timing of formation of micrometastatic lesions in immunodeficient mice transplanted with highly metastatic human breast cancer cells. Next, we clarified that pulmonary fibroblasts acquired high proliferation ability before and after the formation of micrometastases. Furthermore, by DNA microarray analysis of pulmonary fibroblasts isolated from lung tissues before and after micrometastase formation, we discovered the key factors which are activated in pulmonary fibroblasts involved in micrometastase formation.

Free Research Field

幹細胞生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

転移先で増殖したがん細胞は、正常な組織を破壊し、がん患者の予後やQOLに大きな影響を与える。その結果、根治を実現できずに命を失う患者も少なくない。本研究において腫瘍の発生から転移巣形成までの遺伝子発現の変遷を検証したことにより、転移巣形成メカニズムのの解明につながるだけでなく、がん転移において肺の前転移ニッチ形成に寄与する線維芽細胞を標的とした抗転移性の創薬への応用が見込める。将来的には本研究成果に基づき、他のがんの転移機構の解明にも応用し、様々ながん種の抗転移性の治療薬の開発へ応用することも期待できる。