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, accounts for most liver cancer) cells compared to non-CSCs/CICs. In HCC samples, high levels of ANXA3 correlated with expansion of CD1331 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 CD1331 cells, enhancing their tumorigenicity. On the contrary, knockdown of ANXA3 decreased CD1331 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 CD1331 HCC CSCs/CICs in vitro and in vivo. Taken together, these 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 liver cancer.
Pan Q Z, et al. Annexin A3 as a Potential Target for Immunotherapy of Liver Cancer Stem‐Like Cells[J]. Stem Cells, 2015, 33(2): 354-366.