@article{TCR30825,
author = {Qingyu Xu and Ran You and Guowen Yin and Jianping Gu},
title = {Hepatocellular carcinoma serum derived exosomal HIF-1α induces phosphoinositide-3 kinase/protein kinase B signaling to induce the angiogenesis and proliferation of HCC},
journal = {Translational Cancer Research},
volume = {8},
number = {4},
year = {2019},
keywords = {},
abstract = {Background: Tumor exosomes are nanovesicles mostly secreted by tumor cells that play roles of paracrine signaling during tumor progression, including tumor-stromal interactions, activation of proliferative pathways and inducing immunosuppression. The hypoxia-inducible factor (HIF) family serve role of the principal molecular mediators of hypoxia in physiological and pathophysiological course. HIF-1α excreted from tumor and stromal cells serves an important role in tumor angiogenesis, especially in hepatocellular carcinoma (HCC). However, exosomal HIF-1α from HCC serum has not been studied extensively. The present study aimed to determine role of HIF-1α derived from HCC serum exosomes in the development of HCC.
Methods: We extracted exosomes from the serum of 48 patients suffering HCC and 24 healthy individuals. The exosomes were examined by transmission electron microscopy and nanoparticle tracking analysis. The concentrations of exosomal HIF-1α were measured by ELISA. In vitro experiments were performed to testify the exosomal role in human umbilical endothelial cells (HUVECs) and Huh-7 cells by tube formation, cell viability and western blotting analyses. Nude mouse xenograft Huh-7 tumors were generated by injecting HCC patient serum exosomes, healthy individuals’ serum exosomes and PBS into nude mice. Tumors in vivo were isolated, weighed and subjected to immunohistochemical assays.
Results: HCC patients exhibited a greater capacity to convert HIF-1α in serum exosomes than normal individuals (P=0.0007), and high serum exosomal HIF-1α levels were correlated with Barcelona Clinic Liver Cancer (BCLC) staging (P=0.031) and the phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway. The results of flow cytometry analysis demonstrated that the HUVECs cocultured with HCC exosomes turned down the percentage of HUVECs in the G1 phase but turned up the percentage of HUVECs in the S phase (P},
issn = {2219-6803}, url = {https://tcr.amegroups.org/article/view/30825}
}