Cancer stem-like properties of hormonal therapy-resistant breast cancer cells

Kanami Uchiumi, Kouki Tsuboi, Nozomi Sato, Takako Ito, Hisashi Hirakawa, Toshifumi Niwa, Yuri Yamaguchi, Shin ichi Hayashi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Background: Presently, hormonal therapy targeting estrogen receptors is the most effective treatment available for luminal breast cancer. However, many patients relapse after the therapy. It has been suggested that cancer stem-like cells are involved with hormonal therapy resistance; in the present study, we evaluated this hypothesis. Methods: In the present study, we used our previously established hormonal therapy-resistant cell lines, including aromatase inhibitor (AI)-resistant cells (Type 1 and Type 2) and fulvestrant-resistant cells (MFR). Results: AI-resistant cell lines expressing ER (Type 1 V1 and V2) showed high cancer stemness in terms of their CD44/CD24 expression and side populations, which were stimulated by the addition of estrogen and inhibited by fulvestrant. However, ALDH activity was lower than in the ER-negative resistant cells, suggesting that the stemness of luminal cells is distinct from that of basal-like breast cancer cells. The migration and invasion activity of the ER-positive Type 1 V1 and V2 cells were higher than in the ER-negative cell lines, Type 2 and MFR. Conclusions: Fractionation of parental cells based on CD44/CD24 expression and colony formation assay indicated that CD44+/CD24+ cells might be the origin of hormonal therapy-resistant cells. This population reconstituted various other subpopulations under estrogen deprivation. These results indicate that hormonal therapy resistance is closely related to the cancer stem cell-like properties of luminal breast cancer.

Original languageEnglish
Pages (from-to)459-470
Number of pages12
JournalBreast Cancer
Issue number4
Publication statusPublished - 2019 Jul 1


  • Breast cancer
  • Cancer stem-like cells
  • Estrogen receptor
  • Hormonal therapy resistance

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)


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