Understanding heterogeneity within cell population in the process of acquiring anti-cancer drug resistance

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K18359
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology; System genome science
• Research Institution: Toho University (2019); Osaka University (2017-2018)
• Principal Investigator: MAGI Shigeyuki 東邦大学, 医学部, 助教 (90708546)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 乳がん / 薬剤耐性 / １細胞解析

Outline of Final Research Achievements

In order elucidate the biological significance of heterogeneity within the cell population in the process of breast cancer cells acquiring tamoxifen resistance, the author examined cell growth assay and single cell gene expression analysis with MCF-7 breast cancer cells, that were continuously treated with tamoxifen. Cell growth stopped 3 to 6 weeks after administration of tamoxifen, but recovered again after 6 weeks and acquired resistance. A result of single cell gene expression analysis implied that the heterogeneity within cell population increased due to initial response, then decreased due to cell selection, and finally re-increased due to accumulation of genetic mutations. The author revealed that there exist several trajectories toward to two major subpopulations of resistant cells with different characteristics in the background of the heterogeneity.

Free Research Field

システム生物学

Academic Significance and Societal Importance of the Research Achievements

従来の薬剤耐性研究においては、実験手法や結果の解釈の容易さから、野生型株と耐性株を比較する研究手法が主流であった。本研究の成果は、従来型研究で見過ごされてきた耐性獲得の途中過程を経時評価することにより、耐性獲得に伴う不均一性の変化、およびその裏側にある細胞亜集団の複数の出現軌跡を見出した点である。この成果は、複数の軌跡を同時に遮断することで耐性細胞の出現を抑制する新たな治療法の確立につながり、学術的にも社会的にも大きな意義を持つと思われる。