Visualization and Identification of Mechanisms Regulating the Elimination of Metastatic Lung Cancer Cells in the Brain

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16140
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Nagoya University
• Principal Investigator: TSUJI TAKAHIRO 名古屋大学, 医学系研究科, 学振特別研究員(PD) (50850046)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 転移性脳腫瘍

Outline of Final Research Achievements

Metastatic brain tumors have a poor prognosis and severely impact patients' quality of life, making it urgent to understand their pathology. We used two-photon microscopy to visualize lung cancer cells (metastatic brain tumors) and innate immune cells in the brain in vivo. Our findings revealed that lung cancer cells activate the brain's immune system and interact with the microenvironment during their establishment and disappearance. By conducting a temporal expression screening of these establishing cancer cells, we identified factors that allow cancer cells to evade elimination by the microenvironment. Among these, the expression of several “Don’t eat me” signals was found to increase cancer cell colonization rates, serving as key determinants in the metastatic process.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

①領域横断性：肺癌転移性脳腫瘍への対応は呼吸器内科領域だが、疾患は脳神経領域に及び、専門とする研究者は少なかった。この両分野にまたがる、肺癌から転移性脳腫瘍への移行という過程を詳細に観察・記述し、分子機構の一部を明らかにした点で学術的意義がたかい。②転移性脳腫瘍は予後不良の疾患であり、いまだ特異的な治療法・予防法はない。申請者らの発見は、転移性脳腫瘍の発生段階に着目し、その進展・展開を防ぐ分子機構をひとつ見出しているため、これらの治療応用の可能性があり、社会的意義が高い。