Open AccessStemness and anti‐cancer drug resistance in ATP ‐binding cassette subfamily G member 2 highly expressed pancreatic cancer is induced in 3D culture conditions
Author(s) -
Sasaki Norihiko,
Ishiwata Toshiyuki,
Hasegawa Fumio,
Michishita Masaki,
Kawai Hiroki,
Matsuda Yoko,
Arai Tomio,
Ishikawa Naoshi,
Aida Junko,
Takubo Kaiyo,
Toyoda Masashi
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13533
Subject(s) - abcg2 , atp binding cassette transporter , biology , cancer cell , cell culture , cancer research , immunology , cancer , genetics , gene , transporter
The expression of ATP ‐binding cassette subfamily G member 2 ( ABCG 2) is related to tumorigenic cancer stem cells ( CSC ) in several cancers. However, the effects of ABCG 2 on CSC ‐related malignant characteristics in pancreatic ductal adenocarcinoma ( PDAC ) are not well elucidated. In this study, we compared the characteristics of low ( ABCG 2−) and high ( ABCG 2+)‐ ABCG 2‐expressing PDAC cells after cell sorting. In adherent culture condition, human PDAC cells, PANC ‐1, contained approximately 10% ABCG 2+ cell populations, and ABCG 2+ cells displayed more and longer microvilli compared with ABCG 2− cells. Unexpectedly, ABCG 2+ cells did not show significant drug resistance against fluorouracil, gemcitabine and vincristine, and ABCG 2− cells exhibited higher sphere formation ability and stemness marker expression than those of ABCG 2+ cells. Cell growth and motility was greater in ABCG 2− cells compared with ABCG 2+ cells. In contrast, epithelial‐mesenchymal transition ability between ABCG 2− and ABCG 2+ cells was comparable. In 3D culture conditions, spheres derived from ABCG 2− cells generated a large number of ABCG 2+ cells, and the expression levels of stemness markers in these spheres were higher than spheres from ABCG 2+ cells. Furthermore, spheres containing large populations of ABCG 2+ cells exhibited high resistance against anti‐cancer drugs presumably depending on ABCG 2. ABCG 2+ cells in PDAC in adherent culture are not correlated with stemness and malignant behaviors, but ABCG 2+ cells derived from ABCG 2− cells after sphere formation have stemness characteristics and anti‐cancer drug resistance. These findings suggest that ABCG 2− cells generate ABCG 2+ cells and the malignant potential of ABCG 2+ cells in PDAC varies depending on their environments.