Elucidation of the mechanism that separates between normal endometrium aging and cancer development

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19604
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kyushu University
• Principal Investigator: Kato Kiyoko 九州大学, 医学研究院, 教授 (10253527)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 子宮内膜 / 老化 / IL-17RB / IL-6 / IL-8 / IL-1β / オルガノイド

Outline of Final Research Achievements

We have previously reported that IL-17RB is upregulated in the endometrium during aging. We established an IL-17RB-high expressing cell line and demonstrated that IL17B/IL17RB signaling expresses IL6, IL8, and IL1β through the NF-κB pathway. Using organoid formation in primary cultures of normal endometrium, we found that IL-6 and IL-8 increased the formation capacity, IL-1β decreased it, and only IL-1β increased the percentage of SAβgal-positive senescent cells. JNK pathway was extracted as the most relevant factor for IL17RB expression. IL-6 and IL-8 promoted cell proliferation and IL-1β induced cell senescence via JNK pathway. These results indicate that the types of cytokines secreted by senescent cells are involved in the mechanism that separates normal endometrium senescence from cancer development.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

現在日本において晩婚化・晩産化による少子化が問題となっている。この原因として、加齢による卵や子宮内膜の老化による不妊症の増加が挙げられる。また、子宮体癌は罹患率が急増しているが、罹患率は閉経前後より増加してくる。このように加齢による子宮内膜の老化は不妊症や子宮体癌に関与すると考えられる。本研究により子宮内膜は老化により複数の炎症性サイトカインが分泌され、IL-1βは細胞老化、IL-6, IL-8は増殖に関与していることが明らかとなった。前者は着床不全、後者はがん化につながると考えられ、本研究の内容は学術的・社会的に意義がある。