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

Masaki Kawamata, Takeshi Katsuda, Yasuhiro Yamada, Takahiro Ochiya

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)750-757
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume482
Issue number4
DOIs
Publication statusPublished - Jan 22 2017

Fingerprint

Multipotent Stem Cells
Neoplastic Stem Cells
Stem cells
Tumors
Breast Neoplasms
Molecules
Cells
Neoplasms
Cultured Tumor Cells
Vimentin
Drug Resistance
Heterografts
Cell Differentiation
Cell culture
Epithelial Cells
Plasticity
Rats
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

In vitro reconstitution of breast cancer heterogeneity with multipotent cancer stem cells using small molecules. / Kawamata, Masaki; Katsuda, Takeshi; Yamada, Yasuhiro; Ochiya, Takahiro.

In: Biochemical and Biophysical Research Communications, Vol. 482, No. 4, 22.01.2017, p. 750-757.

Research output: Contribution to journalArticle

@article{cdb3829126094133be23edfc5b595d1c,
title = "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.",
author = "Masaki Kawamata and Takeshi Katsuda and Yasuhiro Yamada and Takahiro Ochiya",
year = "2017",
month = "1",
day = "22",
doi = "10.1016/j.bbrc.2016.11.106",
language = "English",
volume = "482",
pages = "750--757",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - In vitro reconstitution of breast cancer heterogeneity with multipotent cancer stem cells using small molecules

AU - Kawamata, Masaki

AU - Katsuda, Takeshi

AU - Yamada, Yasuhiro

AU - Ochiya, Takahiro

PY - 2017/1/22

Y1 - 2017/1/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85007235953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85007235953&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2016.11.106

DO - 10.1016/j.bbrc.2016.11.106

M3 - Article

C2 - 27871860

AN - SCOPUS:85007235953

VL - 482

SP - 750

EP - 757

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -