Abstract 3896: Exosomes derived from CD133+ hepatocellular carcinoma (HCC) cell promote the acquisition of stem cell-like properties of the targeted HCC cell via the Akt/GSK 3β/Snail and cyclin D1 pathways

Abstract

Abstract Backgrounds and Aims: Liver cancer stem cells are closely related to the recurrence and metastasis of hepatocellular carcinoma (HCC). However, the mechanism underlying the reciprocity between liver cancer stem cells and HCC cells in the tumor microenvironment remains unclear. Exosomes act as natural shuttles to deliver bioactive molecules that alter the behavior of the recipient cells, offering a new means of cell-cell communication for physiological and pathological processes in the liver. This study aimed to clarify whether the exosomes derived from the liver stem cells could facilitate the acquisition of stem cell-like properties of the adjacent HCC cells, thereby promoting the malignant process of HCC. Methods: CD133+ liver cancer stem cells were isolated from the highly invasive HCC-LM3 cells or tumor tissues of HCC patients using flow cytometry and were identified using qPCR and immunofluorescence. The exosomes from CD133+ liver cancer stem cells were identified using CD133 and other stem cell markers, and they were then used to treat HepG2 and Hep3B cells. The cell viability, invasion ability, sphere formation and tumorigenesis abilities of the treated HepG2 and Hep3B cells were analyzed to reveal the effect of CD133+ exosomes, and the underlying molecular mechanism was further explored. Results: CD133+ liver cancer stem cells were successfully isolated from HCC-LM3 cells and HCC patients’ tumor tissues, which were able to release CD133+ exosomes. The intake of CD133+ exosomes promoted the putative stem cell phenotype of Hep3B and HepG2 cells, as evidenced by significantly enhanced cell proliferation, invasion and sphere formation abilities in vitro and tumorigenesis in vivo. In additional, we found that CD133+ exosomes activated the PI3K/Akt/GSK3β/Snail and cyclin D1 pathway, thereby reducing the expression of E-Cadherin and promoting the epithelial-mesenchymal transition (EMT) of HCC cells. Conclusions: Our results suggest that exosomes derived from CD133+ HCC cells can change the malignant behavior and promote the acquisition of stem cell-like properties of targeted HCC cells via the Akt/GSK 3β/Snail and cyclin D1 pathways. Note: This abstract was not presented at the meeting. Citation Format: Pengyi Guo, Haitao Yu, Xiaozhai Xie, Yi Wang, Gang Chen. Exosomes derived from CD133+ hepatocellular carcinoma (HCC) cell promote the acquisition of stem cell-like properties of the targeted HCC cell via the Akt/GSK 3β/Snail and cyclin D1 pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3896. doi:10.1158/1538-7445.AM2017-3896