Identification and Functional Analysis of EPOR+ Tumor-Associated Macrophages in Human Osteosarcoma Lung Metastasis
Background. Tissue-resident macrophages can be educated to tumor-associated macrophages (TAMs) by the tumor microenvironment and many types of macrophages express erythropoietic receptor (EPOR); However, little is known about the expression of EPOR on TAMs and the identity of EPOR+ TAMs in osteosarc...
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| Format: | Article |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/9374240 |
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| author | Yanxing Li Ming Li Rong Wei Junlong Wu |
| author_facet | Yanxing Li Ming Li Rong Wei Junlong Wu |
| author_sort | Yanxing Li |
| collection | DOAJ |
| description | Background. Tissue-resident macrophages can be educated to tumor-associated macrophages (TAMs) by the tumor microenvironment and many types of macrophages express erythropoietic receptor (EPOR); However, little is known about the expression of EPOR on TAMs and the identity of EPOR+ TAMs in osteosarcoma lung metastasis has thus far remained elusive. Methods. EPOR-eGFPcre mice were used to determine the expression of EPOR on lung tissue-resident macrophages. Flow cytometry, RT-PCR, and Western blot were examined to define the identity of EPOR+ TAMs in 106 osteosarcoma lung metastasis specimens. Moreover, the clinicopathologic factors and prognosis of patients with CD163+EPOR+ macrophages were compared. Results. We found that a subpopulation of mouse lung tissue-resident macrophages express EPOR and EPO enhances the proliferation of EPOR+ macrophages in mouse lung. A subpopulation of CD163+ macrophages expresses EPOR in human osteosarcoma lung metastasis specimens. CD163+EPOR+TAMs increase 2.5 times in human osteosarcoma lung metastasis tissues; CD206, CD163, and PD1, which are known to have a significant role in TAM function had high expression in CD163+EPOR+ TAMs compared with CD163+EPOR- TAMs. Furthermore, CD163+EPOR+ TAMs had higher M2 marker and cytokine expression in osteosarcoma tissues compared with para-osteosarcoma tissues. EPO enhanced the expression of M2 cytokines in primary CD163+EPOR+ TAMs. Importantly, the percentage of CD163+EPOR+ TAMs had a positive linear association with malignant phenotypes as well as poor disease-free survival and overall survival time. Conclusions. We have characterized TAMs expressing EPOR and CD163+EPOR+ macrophages as TAMs in osteosarcoma lung metastasis patients, which are highly associated with tumor aggressiveness. |
| format | Article |
| id | doaj-art-fbff10031ea24d43894ba3efb35fda35 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-fbff10031ea24d43894ba3efb35fda352025-02-03T01:01:55ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/93742409374240Identification and Functional Analysis of EPOR+ Tumor-Associated Macrophages in Human Osteosarcoma Lung MetastasisYanxing Li0Ming Li1Rong Wei2Junlong Wu3Department of Orthopedic Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, ChinaDepartment of Orthopedic Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, ChinaDepartment of Orthopedic Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, ChinaDepartment of Orthopedic Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, ChinaBackground. Tissue-resident macrophages can be educated to tumor-associated macrophages (TAMs) by the tumor microenvironment and many types of macrophages express erythropoietic receptor (EPOR); However, little is known about the expression of EPOR on TAMs and the identity of EPOR+ TAMs in osteosarcoma lung metastasis has thus far remained elusive. Methods. EPOR-eGFPcre mice were used to determine the expression of EPOR on lung tissue-resident macrophages. Flow cytometry, RT-PCR, and Western blot were examined to define the identity of EPOR+ TAMs in 106 osteosarcoma lung metastasis specimens. Moreover, the clinicopathologic factors and prognosis of patients with CD163+EPOR+ macrophages were compared. Results. We found that a subpopulation of mouse lung tissue-resident macrophages express EPOR and EPO enhances the proliferation of EPOR+ macrophages in mouse lung. A subpopulation of CD163+ macrophages expresses EPOR in human osteosarcoma lung metastasis specimens. CD163+EPOR+TAMs increase 2.5 times in human osteosarcoma lung metastasis tissues; CD206, CD163, and PD1, which are known to have a significant role in TAM function had high expression in CD163+EPOR+ TAMs compared with CD163+EPOR- TAMs. Furthermore, CD163+EPOR+ TAMs had higher M2 marker and cytokine expression in osteosarcoma tissues compared with para-osteosarcoma tissues. EPO enhanced the expression of M2 cytokines in primary CD163+EPOR+ TAMs. Importantly, the percentage of CD163+EPOR+ TAMs had a positive linear association with malignant phenotypes as well as poor disease-free survival and overall survival time. Conclusions. We have characterized TAMs expressing EPOR and CD163+EPOR+ macrophages as TAMs in osteosarcoma lung metastasis patients, which are highly associated with tumor aggressiveness.http://dx.doi.org/10.1155/2020/9374240 |
| spellingShingle | Yanxing Li Ming Li Rong Wei Junlong Wu Identification and Functional Analysis of EPOR+ Tumor-Associated Macrophages in Human Osteosarcoma Lung Metastasis Journal of Immunology Research |
| title | Identification and Functional Analysis of EPOR+ Tumor-Associated Macrophages in Human Osteosarcoma Lung Metastasis |
| title_full | Identification and Functional Analysis of EPOR+ Tumor-Associated Macrophages in Human Osteosarcoma Lung Metastasis |
| title_fullStr | Identification and Functional Analysis of EPOR+ Tumor-Associated Macrophages in Human Osteosarcoma Lung Metastasis |
| title_full_unstemmed | Identification and Functional Analysis of EPOR+ Tumor-Associated Macrophages in Human Osteosarcoma Lung Metastasis |
| title_short | Identification and Functional Analysis of EPOR+ Tumor-Associated Macrophages in Human Osteosarcoma Lung Metastasis |
| title_sort | identification and functional analysis of epor tumor associated macrophages in human osteosarcoma lung metastasis |
| url | http://dx.doi.org/10.1155/2020/9374240 |
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