Analysis of a candidate gene for breast cancer stemness

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10569
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Research Institute for Clinical Oncology, Saitama Cancer Center
• Principal Investigator: Takai Ken 埼玉県立がんセンター(臨床腫瘍研究所), 病院 乳腺腫瘍内科, その他 (80775031)
• Co-Investigator(Kenkyū-buntansha): 永井 成勲 埼玉県立がんセンター(臨床腫瘍研究所), 病院 乳腺腫瘍内科, 副部長 (20458277)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 乳癌 / 膜型エストロゲン受容体 / 癌幹細胞 / 血液循環腫瘍細胞

Outline of Final Research Achievements

To develop the breast cancer stem cell-targeted therapy, we first examined the expressions of LGR5, one of mammary stem cell markers, and estrogen receptor (ER), a target of hormone therapy, in breast cancer tissues. Although ER was expressed in the nucleus of LGR5(-), not LGR5(+), tumor cells at the tumor cluster site, there were LGR5(+) tumor cells with membrane-localized ERs (mERs) at the stromal site. The mER-expressing tumor cells were also detected in the pleural effusion and the blood of hormone receptor-positive breast cancer patients. The detection of mER cells in patients’ blood was useful for prediction of the efficacy of the first hormone therapy, and changes of their numbers were correlated with therapy response. We found that LGR5(+) cells finally increased in a case of resistance to the therapy. Thus, although we could not demonstrate that LGR5 was a breast cancer stem cell marker, it may be related with therapy resistance.

Free Research Field

腫瘍細胞生物学

Academic Significance and Societal Importance of the Research Achievements

転移・再発ホルモン受容体陽性乳癌における血中mERの検出は、一次治療として副作用の少ない内分泌療法を選択できることを示しており、患者に負担の少ないリキッドバイオプシーが転移部位の生検に代わる可能性がある。LGR5(+)細胞が乳癌幹細胞の可能性を示唆する状況証拠はあるものの、LGR5(-)細胞からも誘導される可能性が示唆された。癌幹細胞仮説を柔軟に取り入れて研究を進めることが腫瘍生物学の理解に重要と考えられた。