To elucidate niche factors promoting micro liver metastasis of pancreatic cancer using genetically engineered model mice.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16566
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: SADA Masafumi 九州大学, 医学研究院, 共同研究員 (10783508)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 膵癌 / 微小環境 / 微小転移 / 癌関連線維芽細胞 / 好中球 / NETs / CD110

Outline of Final Research Achievements

Present study using pancreatic cancer spontaneous mice (KPC mice) and a splenic instilled liver metastasis model revealed that cancer-associated fibroblasts (CAF) are concentrated around cancer cells in the liver metastasis. It was suggested that CAFs construct micro environment which promoting liver metastasis formation. Furthermore, we focused on the concentration of neutrophils prior to CAFs and found that a mechanism called neutrophil extra-traps (NETs) work to promote liver metastasis formation.
In addition, liver metastasis was significantly increased when CD110 expression in cancer cells was high level, and it was shown that CD110 expression may be involved in liver metastasis formation of pancreatic cancer.
From these results, it is suggested that CAFs and neutrophils are involved on the host side and CD110 expression on the cancer side as factors that promote the formation of micro liver metastases of pancreatic cancer.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

固形癌の多くは、進行すると遠隔臓器への転移をきたして致命的となることが多い。中でも膵癌は5年生存率が10％に満たず、その治療成績改善は急務である。
膵癌の進行過程において、肝転移をはじめとした遠隔転移の形成は非常に重要な局面であり、転移形成を制御することができれば、予後改善のための大きな一歩となり得る。本研究では膵癌の肝転移におけるごく初期段階に関する詳細な検討を行い、宿主側と癌側での新たな促進因子を見出すことができた。これらの結果は、今後の膵癌の治療成績向上に繋がると考えられる。