Interaction of protumor stromal cells accelerates cancer progression

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04691
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Akita University
• Principal Investigator: Tanaka Masamitsu 秋田大学, 医学系研究科, 教授 (20291396)
• Research Collaborator: KURIYAMA SEI ; ITOH GO
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: がん間質 / 癌関連線維芽細胞 / 腫瘍随伴マクロファージ / 中皮細胞 / 細胞外小胞 / 情報伝達

Outline of Final Research Achievements

It is not well understood how Tumor-derived extracellular vesicles (TEVs) are delivered and effect on stromal cells in a tumor microenvironment. We identified a novel function of macrophages in delivery and transmission of TEVs. TEV incorporated macrophages (TEV-MΦ) increased invasion and widely disseminated. Upon contact with host stromal cells including mesothelial cells (MC), fibroblasts and endothelial cells, TEV-MΦs released membrane blebs containing TEVs. Then, scattered blebs were incorporated in these stromal cells, which transferred tumor-derived proteins and RNAs. Macrophage mediated transfer of TEVs caused myofibroblastic change in the recipient cells. In TEV-MΦ injected mice stomach, TEVs were delivered by MΦs to MCs covering the stomach, and MCs entered the gastric wall to create a niche that favored invasion of gastric cancer cells. These findings suggest a novel function of TAMs that transfer TEVs to surrounding stromal cells and increase CAF-like cells.

Free Research Field

腫瘍生物

Academic Significance and Societal Importance of the Research Achievements

癌をサポートする様々な間質細胞の形質転換が広範囲に起きる事は、やがて癌細胞の浸潤を招く場を形成する。MΦが癌の情報を周辺のヘテロな間質細胞に伝搬していくメカニズムの一端を明らかにした事で、癌細胞とサポーター的な間質細胞間のネットワークを遮断し、癌の広がりを未然に防ぐ治療方針の基盤となる。今後特に化療後の再燃、憎悪の経過をとる症例で治療標的や予測分子が見出される事が期待される。