In:
Stem Cells, Oxford University Press (OUP), Vol. 33, No. 2 ( 2015-02-01), p. 354-366
Abstract:
Cancer stem-like cells/cancer-initiating cells (CSCs/CICs) are considered to represent a small population of cancer cells that is resistant to conventional cancer treatments and responsible for tumor recurrence and metastasis. The aim of this study was to establish CSC/CIC-targeting immunotherapy. In this study, we found that Annexin A3 (ANXA3) was preferentially expressed in CSCs/CICs derived from hepatocellular carcinoma (HCC) cells compared to non-CSCs/CICs. In HCC samples, high levels of ANXA3 correlated with expansion of CD133+ tumor cells representing CSCs/CICs in HCC; the combination of high levels of ANXA3 and CD133 was associated with progression of HCC. Overexpression of ANXA3 increased the proportion of CD133+ cells, enhancing their tumorigenicity. On the contrary, knockdown of ANXA3 decreased CD133+ cells and inhibited tumorigenicity. The mechanistic study revealed that ANXA3-mediated maintenance of HCC CSCs/CICs activity was likely involved with the HIF1A/Notch pathway. Using ANXA3 as a target, ANXA3-transfected dendritic cells could induce more functionally active T cells and these effector T cells could superiorly kill CD133+ HCC CSCs/CICs in vitro and in vivo. Taken together, our findings suggest that ANXA3 plays a role in HCC CSC/CIC maintenance, and that ANXA3 may represent a potential CSC/CIC-specific therapeutic target for improving the treatment of HCC. Stem Cells 2015;33:354–366
Type of Medium:
Online Resource
ISSN:
1066-5099
,
1549-4918
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2015
detail.hit.zdb_id:
2030643-X
detail.hit.zdb_id:
1143556-2
detail.hit.zdb_id:
605570-9
SSG:
12
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