Investigation of cancer stem-like properties of ovarian cancer cells associated with the floating mesothelium

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09669
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Osaka University
• Principal Investigator: Shishido Akemi 大阪大学, 大学院医学系研究科, 招へい研究員 (30838909)
• Co-Investigator(Kenkyū-buntansha): 山本 浩文 大阪大学, 大学院医学系研究科, 教授 (30322184) ; 横山 雄起 大阪大学, 大学院医学系研究科, 助教 (60615714)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 卵巣癌 / 浮遊播種病変 / 癌幹細胞

Outline of Final Research Achievements

Ovarian cancer cells often produce spheroid formation in abdominal cavity. It is, however, largely unrevealed how peritoneal dissemination of ovarian cancer cells is established and why some tumor cell population is resistant to chemotherapy. In this study, we worked on this problem in terms of cancer stem-like properties which is thought to be one of the reasons for chemo-resistance. Using a cancer stem cell model that can produce tumor in mice from a single cell, we took notice of LYPD3 among various up-regulated genes. LYPD3 level increased in spheroid cultures. Overexpression of LYPD3 cDNA led to induction of cancer stem markers such as CD44v9 and ALDH1A1. These findings suggest that LYPD3 may be a novel marker for ovarian cancer spheroids.

Free Research Field

病理学、細胞診断学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

卵巣癌はしばしば腹腔内に浮遊する癌細胞の集塊をつくる。これは腹膜播種の中でも独特の形態でありスフェロイドと呼ばれ、治療抵抗性の癌幹細胞との関連が示唆されている。本研究課題では、卵巣癌の癌幹細胞マーカーとしてLYPD3という分子を見出した。LYPD3は癌細胞の細胞膜上に存在するGPIアンカー型の膜蛋白であり、大腸癌の転移・再発にも関係していることが分かっている。本研究成果はLYPD3に対する新しい抗体治療の可能性に繋がるもので学術的、医学的意義は大きい。