Uterine Leiomyosarcoma Target Factor Identification and Application

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K11299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nippon Medical School
• Principal Investigator: Terasaki Mika 日本医科大学, 医学部, 講師 (50372785)
• Co-Investigator(Kenkyū-buntansha): 永坂 真也 日本医科大学, 医学部, 助教 (00573239) ; 寺崎 泰弘 日本医科大学, 医学部, 准教授 (50332870)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 子宮平滑筋肉腫 / 骨芽細胞分化 / RUNX2 / 腎癌 / 肺癌 / 破骨細胞様巨細胞

Outline of Final Research Achievements

In the present study, we discovered that tumor cells of uterine leiomyosarcoma with osteoclast-like giant cells (LMS with OLGCs) express RUNX2 and osteoblast-related markers. This suggests that LMS with OLGCs represents a distinct subtype of LMS, characterized by osteoblastoid differentiation. Notably, OLGCs, a defining feature of this tumor type, derived from infiltrating macrophages into osteoclasts. These osteoclasts subsequently degrade and eliminate surrounding type IV collagen fibers, leading to a tumor tissue that is prone to hemorrhage. Furthermore, we observed RUNX2 expression in tumors of other organs without evidence of osteogenesis or osteoclast-like giant cells. We also delineated the localization of RUNX2 expression in lung and kidney cancers, where RUNX2 has been identified as a poor prognostic indicator. Consequently, RUNX2 may serve as a potential therapeutic target not only for uterine leiomyosarcoma, but also for these diseases with poor prognostic outcomes.

Free Research Field

腫瘍病理

Academic Significance and Societal Importance of the Research Achievements

本研究は、高悪性度の婦人科腫瘍および肺癌、腎癌におけるＲＵＮＸ２および骨芽細胞分化マーカーの発現は、現在まで治療が困難で、予後不良であった症例の治療ターゲットになり得る可能性を示した。これまで、骨芽細胞にしか起こらないと考えられていた分化課程は、高悪性度肉腫や低分化および未分化な癌細胞にも生じていることが示唆され、骨芽細胞分化を起こした腫瘍という臓器を超えた疾患カテゴリーの創出と、治療戦略になりえる発見であったことに社会的意義がある。