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- Title
Annexin A3 as a Potential Target for Immunotherapy of Liver Cancer Stem-Like Cells.
- Authors
Pan, Qiu-Zhong; Pan, Ke; Wang, Qi-Jing; Weng, De-Sheng; Zhao, Jing-Jing; Zheng, Hai-Xia; Zhang, Xiao-Fei; Jiang, Shan-Shan; Lv, Lin; Tang, Yan; Li, Yong-Qiang; He, Jia; Liu, Qing; Chen, Chang-Long; Zhang, Hong-Xia; Xia, Jian-Chuan
- 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. S tem C ells 2015;33:354-366
- Subjects
ANNEXINS; IMMUNOTHERAPY; LIVER cancer; CANCER stem cells; DENDRITIC cells; GENE expression
- Publication
Stem Cells, 2015, Vol 33, Issue 2, p354
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.1850