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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.

cancer science

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