Reprogramming study of endometrial cancer cells for restoring fertility

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09272
• 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: Keio University
• Principal Investigator: YANOKURA Megumi 慶應義塾大学, 医学部(信濃町), 特任助教 (20433732)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 子宮体癌 / リプログラミング / 着床阻害 / カルシウムシグナルパスウェイ

Outline of Final Research Achievements

Clinical observations have confirmed that implantation does not occur in patients with endometrial cancer. The mechanism of acquisition of phenotypes characteristic of cancer cells can be examined by identifying epigenomic changes during reprogramming. Therefore, we first produced reprogrammed cancer (RC) cells from human endometrial cancer cell lines. DNA methylation and changes in gene expression and implantation capacity in these cells were then examined to explore the mechanism of inhibition of implantation in endometrial cancer.
Upregulation of undifferentiated markers and decreased cell proliferation were observed in the RC cells. The in vitro implantation test showed significantly increased implantation capacity in RC cells compared with parent cell lines (p<0.05). DNA methylation array analysis showed significant differences in methylation (31,511/747,192, 4.2%) in parent and RC cells (p<0.05, |β|>0.25). A calcium signaling pathway was identified by KEGG enrichment analysis.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

今までのところ、子宮体癌細胞を用いたリプログラミングの報告はなく、既存の方法でリプログラミング可能であったことは学術的に意義がある。
また、リプログラミングによって正常子宮内膜細胞において着床に重要な役割を担っている遺伝子の発現が回復したことが明らかになった。子宮体癌細胞において、これらの遺伝子発現を回復させることで癌の性質や着床能に変化が認められれば、妊孕性温存・回復治療に寄与する可能性がある。