In vitro reconstitution of breast cancer heterogeneity with multipotent cancer stem cells using small molecules

Masaki Kawamata, Takeshi Katsuda, Yasuhiro Yamada, Takahiro Ochiya

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

A small fraction of tumor cells are thought to possess the potential for both multiple-lineage differentiation and self-renewal, which underlies the cancer stem cell hypothesis. However, the differentiation mechanisms of these cells have not been elucidated due to a lack of appropriate culture methods. Here, we established a culture condition for maintaining multipotent tumor cells from rat breast tumors using 4 small molecules. Cultured tumor cells in this condition retained their intrinsic myoepithelial features, expressing p63 and CK14 and vimentin. In a xenograft model, the p63-expressing cells formed epithelial tumors containing glandular, squamous and sebaceous compartments. Upon withdrawal of the small molecules, p63 and CK14 expression was lost, with concurrent increase in expression of mesenchymal markers. These transited cells acquired drug resistance and invasiveness and showed massive sarcomatoid tumorigenicity. Epithelial features could not be recovered by re-exposure to the small molecules in the transited cells. Here, we have identified multipotent cancer cells within primary mammary tumors and demonstrated that their plasticity is maintained by the small molecules.

本文言語英語
ページ(範囲)750-757
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
482
4
DOI
出版ステータス出版済み - 1 22 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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