B7H3 as a promising therapeutic target for endometrial cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09769
• 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: Hokkaido University
• Principal Investigator: Ihira Kei 北海道大学, 医学研究院, 特任助教 (50813820)
• Co-Investigator(Kenkyū-buntansha): 董 培新 北海道大学, 医学研究院, 特任助教 (50602504)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: B7H3 / 子宮体癌

Outline of Final Research Achievements

The new immune checkpoint molecule B7H3 reduces the capacity of immune cells to target cancer cells and leads to cancer progression. Using our previously established highly invasive subline and cancer stem cell-like sphere cells and the CRISPR/Cas9 method, we attempted to elucidate the role of B7H3 in the acquisition of malignant features in endometrial cancer cells as well as the regulatory mechanism of B7H3 expression by CTDSPL, miR-199a, and mutant p53. Down-regulation of the CTDSPL gene and miR-199a, as well as mutant p53, all contribute to the acquisition of malignant features in endometrial cancer cells by increasing B7H3 expression and activating downstream PI3K/AKT and STAT3 pathways, implying that B7H3 is a novel therapeutic target for endometrial cancer. According to our results, B7H3 may be a potential therapeutic target for endometrial cancer.

Free Research Field

婦人科癌

Academic Significance and Societal Importance of the Research Achievements

体癌は最も頻度の高い婦人科悪性腫瘍の一つであり、患者数(特に若い世代)は年々増加傾向にある。体癌の進展に関わる分子基盤は十分には理解されておらず、依然として有望な創薬標的分子の同定は急務である。そこで、体癌において、癌の進展の促進に重要な役割を果たすB7H3を見出して、その関連分子経路を解明した。今後B7H3を標的することで、体癌細胞の転移能を阻害することができれば、体癌の新しい治療法を創出する可能性がある。