論文

査読有り 国際誌
2018年4月

Stemness and anti-cancer drug resistance in ATP-binding cassette subfamily G member 2 highly expressed pancreatic cancer is induced in 3D culture conditions.

Cancer science
  • Norihiko Sasaki
  • ,
  • Toshiyuki Ishiwata
  • ,
  • Fumio Hasegawa
  • ,
  • Masaki Michishita
  • ,
  • Hiroki Kawai
  • ,
  • Yoko Matsuda
  • ,
  • Tomio Arai
  • ,
  • Naoshi Ishikawa
  • ,
  • Junko Aida
  • ,
  • Kaiyo Takubo
  • ,
  • Masashi Toyoda

109
4
開始ページ
1135
終了ページ
1146
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/cas.13533

The expression of ATP-binding cassette subfamily G member 2 (ABCG2) is related to tumorigenic cancer stem cells (CSC) in several cancers. However, the effects of ABCG2 on CSC-related malignant characteristics in pancreatic ductal adenocarcinoma (PDAC) are not well elucidated. In this study, we compared the characteristics of low (ABCG2-) and high (ABCG2+)-ABCG2-expressing PDAC cells after cell sorting. In adherent culture condition, human PDAC cells, PANC-1, contained approximately 10% ABCG2+ cell populations, and ABCG2+ cells displayed more and longer microvilli compared with ABCG2- cells. Unexpectedly, ABCG2+ cells did not show significant drug resistance against fluorouracil, gemcitabine and vincristine, and ABCG2- cells exhibited higher sphere formation ability and stemness marker expression than those of ABCG2+ cells. Cell growth and motility was greater in ABCG2- cells compared with ABCG2+ cells. In contrast, epithelial-mesenchymal transition ability between ABCG2- and ABCG2+ cells was comparable. In 3D culture conditions, spheres derived from ABCG2- cells generated a large number of ABCG2+ cells, and the expression levels of stemness markers in these spheres were higher than spheres from ABCG2+ cells. Furthermore, spheres containing large populations of ABCG2+ cells exhibited high resistance against anti-cancer drugs presumably depending on ABCG2. ABCG2+ cells in PDAC in adherent culture are not correlated with stemness and malignant behaviors, but ABCG2+ cells derived from ABCG2- cells after sphere formation have stemness characteristics and anti-cancer drug resistance. These findings suggest that ABCG2- cells generate ABCG2+ cells and the malignant potential of ABCG2+ cells in PDAC varies depending on their environments.

リンク情報
DOI
https://doi.org/10.1111/cas.13533
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29444383
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891171