Open AccessAnnexin A3 as a Potential Target for Immunotherapy of Liver Cancer Stem‐Like Cells
Author(s) -
Pan QiuZhong,
Pan Ke,
Wang QiJing,
Weng DeSheng,
Zhao JingJing,
Zheng HaiXia,
Zhang XiaoFei,
Jiang ShanShan,
Lv Lin,
Tang Yan,
Li YongQiang,
He Jia,
Liu Qing,
Chen ChangLong,
Zhang HongXia,
Xia JianChuan
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1850
Subject(s) - biology , stem cell , cancer stem cell , cancer research , liver cancer , immunotherapy , cancer , immunology , microbiology and biotechnology , genetics , hepatocellular carcinoma
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. S tem C ells 2015;33:354–366