Side population cells in human gallbladder cancer cell line GBC-SD regulated by TGF-β-induced epithelial-mesenchymal transition.
- Author:
Zhifa, ZHANG
;
Feng, ZHU
;
Ling, XIAO
;
Min, WANG
;
Rui, TIAN
;
Chengjian, SHI
;
Renyi, QIN
- Publication Type:Journal Article
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2011;31(6):749-55
- CountryChina
- Language:English
-
Abstract:
Mounting evidence has shown that side population (SP) cells are enriched for cancer stem cells (CSCs) responsible for cancer malignancy. In this study, SP technology was used to isolate a small subpopulation of SP cells in human gallbladder cancer cell line GBC-SD, and SP cells which had superior potential for proliferation in vitro and tumorigenesis in vivo were identified. Importantly, the abundance of GBC-SD SP cells was increased by a transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT), and this effect was accompanied with a strong up-regulation of ABCG2 mRNA expression, and a decreased sensitivity to mitoxantrone. SP cells were restored upon the removal of TGF-β and the reversion of the cells to an epithelial phenotype, and smad3-specific siRNA reduced SP abundance in response to TGF-β. In conclusion, TGF-β-induced EMT by smad-dependent signaling pathway promotes cancer development and anti-cancer drug resistant phenotype by augmenting the abundance of GBC-SD SP cells, and a better understanding of mechanisms involved in TGF-β-induced EMT may provide a novel strategy for preventing cancer progression.
