Annexin A3 as a potential target for immunotherapy of liver cancer stem-like cells.

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.

• Authors: Qiu-Zhong Pan, Ke Pan, Qi-Jing Wang, De-Sheng Weng, Jing-Jing Zhao, Hai-Xia Zheng, Xiao-Fei Zhang, Shan-Shan Jiang, Lin Lv, Yan Tang, Yong-Qiang Li, Jia He, Qing Liu, Chang-Long Chen, Hong-Xia Zhang, Jian-Chuan Xia
• Journal: Stem cells (Dayton, Ohio) (Stem Cells) Vol. 33 Issue 2 Pg. 354-66 (Feb 2015) ISSN: 1549-4918 [Electronic] England
• PMID: 25267273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 AlphaMed Press.

Chemical References

• AC133 Antigen
• Antigens, CD
• Glycoproteins
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Neoplasm Proteins
• PROM1 protein, human
• Peptides
• Prom1 protein, mouse
• Receptors, Notch
• Annexin A3

Topics

• AC133 Antigen
• Animals
• Annexin A3 (genetics, immunology)
• Antigens, CD (genetics, immunology)
• Dendritic Cells (immunology, pathology)
• Glycoproteins (genetics, immunology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, immunology)
• Immunotherapy
• Liver Neoplasms (genetics, immunology, pathology, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Proteins (genetics, immunology)
• Neoplastic Stem Cells (immunology, pathology)
• Peptides (genetics, immunology)
• Receptors, Notch (genetics, immunology)
• T-Lymphocytes (immunology, pathology)
• Transfection