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Cancer Cell International
Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor

Authors: Shuo Miao, Su-Mei Wang, Xue Cheng, Yao-Feng Li, Qing-Song Zhang, Gang Li, Song-Qing He, Xiao-Ping Chen, Ping Wu

Published in: Cancer Cell International | Issue 1/2017

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Abstract

Background

Erythropoietin (EPO) is a hypoxia-inducible stimulator of erythropoiesis. Besides its traditional application in anemia therapy, it offers an effective treatment in the cancer patients, especially those who receive chemotherapy. Several reports indicated that it could promote the tumor cell proliferation through its specific receptor (EPOR). Unfortunately, the role of EPO/EPOR in hepatocellular carcinoma (HCC) progressing is still uncertain.

Methods

Protein in tumor tissue from HCC patients or H22 tumor-bearing mice was detected with immunohistochemistry. Cells were cultured under 1% oxygen to establish hypoxia. RT-PCR and western blotting were used to measure mRNA and protein of EPO/EPOR, respectively. MTT, flow cytometry and PCNA staining were used to detect cell proliferation. Immunofluorescence staining was applied to study the expression and location of cellular EPOR. The EPOR binding studies were performed with 125I-EPO radiolabeling assay.

Results

EPO and EPOR protein were up-regulated in HCC tissue of patients and H22-bearing mice. These were positively correlated with hypoxia-inducible factor -1 α and ki-67. Hypoxia up-regulated the expression of EPO and EPOR in HepG2 cells. It also induced the proliferation and increased the percentage of divided cells after 24, 48 and 72 h treatment. These were inhibited in cells pre-treated with 0.5 μg/mL soluble-EPOR. Immunofluorescence staining presented that EPOR was obviously translocated from nucleus to cytoplasm and membrane under hypoxia. EPOR binding activity was also increased after exposure to hypoxia. Recombinant human erythropoietin obviously elevated cell proliferation rate and the percentage of divided under hypoxia but not normoxia, which were also inhibited by soluble-EPOR.

Conclusions

Our result indicated for the first time that EPO promoted the proliferation of HCC cells through hypoxia induced translocation of it specific receptor.
Trial registration TJC20141113, retrospectively registered
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Metadata
Title
Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor
Authors
Shuo Miao
Su-Mei Wang
Xue Cheng
Yao-Feng Li
Qing-Song Zhang
Gang Li
Song-Qing He
Xiao-Ping Chen
Ping Wu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0494-7

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