Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor
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...
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-017-0494-7 |
| _version_ | 1819169667749511168 |
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| author | Shuo Miao Su-Mei Wang Xue Cheng Yao-Feng Li Qing-Song Zhang Gang Li Song-Qing He Xiao-Ping Chen Ping Wu |
| author_facet | Shuo Miao Su-Mei Wang Xue Cheng Yao-Feng Li Qing-Song Zhang Gang Li Song-Qing He Xiao-Ping Chen Ping Wu |
| author_sort | Shuo Miao |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-22T19:23:09Z |
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| id | doaj.art-1cf733f855f34bc3b203d4a4e52d4451 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-22T19:23:09Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-1cf733f855f34bc3b203d4a4e52d44512022-12-21T18:15:19ZengBMCCancer Cell International1475-28672017-12-0117111410.1186/s12935-017-0494-7Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptorShuo Miao0Su-Mei Wang1Xue Cheng2Yao-Feng Li3Qing-Song Zhang4Gang Li5Song-Qing He6Xiao-Ping Chen7Ping Wu8Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathophysiology, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathophysiology, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathophysiology, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnolgyDepartment of Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical UniversityHepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnolgyDepartment of Pathophysiology, Tongji Medical College, Huazhong University of Science and TechnologyAbstract 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 registeredhttp://link.springer.com/article/10.1186/s12935-017-0494-7ErythropoietinErythropoietin receptorHepatocellular carcinomaHypoxiaProliferation |
| spellingShingle | Shuo Miao Su-Mei Wang Xue Cheng Yao-Feng Li Qing-Song Zhang Gang Li Song-Qing He Xiao-Ping Chen Ping Wu Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor Cancer Cell International Erythropoietin Erythropoietin receptor Hepatocellular carcinoma Hypoxia Proliferation |
| title | Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor |
| title_full | Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor |
| title_fullStr | Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor |
| title_full_unstemmed | Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor |
| title_short | Erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor |
| title_sort | erythropoietin promoted the proliferation of hepatocellular carcinoma through hypoxia induced translocation of its specific receptor |
| topic | Erythropoietin Erythropoietin receptor Hepatocellular carcinoma Hypoxia Proliferation |
| url | http://link.springer.com/article/10.1186/s12935-017-0494-7 |
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