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

Abstract：

: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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kawamata M,Katsuda T,Yamada Y,Ochiya T

doi

10.1016/j.bbrc.2016.11.106

subject

Has Abstract

pub_date

2017-01-22 00:00:00

pages

750-757

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)31980-5

journal_volume

482

pub_type

杂志文章

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