Analysis of Survival and Reactivating Factors in Tumor Cells during Metastatic Latency in Bone

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09403
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Hokkaido University
• Principal Investigator: Arai Ryuta 北海道大学, 医学研究院, 客員研究員 (40722509)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 転移性骨腫瘍 / 転移性潜在期

Outline of Final Research Achievements

Bone metastasis often arises years after the removal of the early-staged primary cancer. This clinical time interval is known as metastatic latency. Since a regulator of tumor cells during the metastatic latency has been unknown, preventative therapeutic strategies have not been developed but required.
To this, we created in vivo models of bone metastasis with latency periods. After selecting the upregulated genes in the latency subline, a further screening was performed on clinical transcriptome data: early-staged cancer annotated with subsequent bone metastasis. It successfully narrowing down the most independent factor for the poor prognosis.
Validation was conducted using the knock doown cell lines and a related pathway inhibitors. Moreover, immunohistopathology in clinical samples revealed that the positive rates of the regulator were correlated positively with bone metastasis.

Free Research Field

癌

Academic Significance and Societal Importance of the Research Achievements

癌による死亡の90%は転移に関連している。転移性腫瘍に対する予防として、遠隔臓器に播種後の、潜伏期における細胞の生存と再活性化のステップを標的とすることが効果的であると考えられている。しかしながら、骨における潜伏期腫瘍細胞の生存・再活性化メカニズムや制御因子は依然不明であり、治療薬開発には至っていない
それに対し本研究では転移性骨腫瘍マウスモデルを確立、潜伏期腫瘍細胞細胞株を樹立し分子生物学的解析を行い、転移巣での制御因子の同定、その関連経路に基づく新規骨転移予防薬の確立を行った。
これにより、転移性腫瘍に対する新たな予防・治療戦略が開かれた。