Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling
The interleukin-22 (IL-22) signaling pathway is well known to be involved in the progression of various cancer types but its role in bone metastatic breast cancer remains unclear. We demonstrate using human GEO profiling that bone metastatic breast cancer displays elevated interleukin-22 receptor 1...
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MDPI AG
2020-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/1/131 |
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| author | Eun-Young Kim Bongkun Choi Ji-Eun Kim Si-On Park Sang-Min Kim Eun-Ju Chang |
| author_facet | Eun-Young Kim Bongkun Choi Ji-Eun Kim Si-On Park Sang-Min Kim Eun-Ju Chang |
| author_sort | Eun-Young Kim |
| collection | DOAJ |
| description | The interleukin-22 (IL-22) signaling pathway is well known to be involved in the progression of various cancer types but its role in bone metastatic breast cancer remains unclear. We demonstrate using human GEO profiling that bone metastatic breast cancer displays elevated interleukin-22 receptor 1 (IL-22R1) and sphingosine-1-phosphate receptor 1 (S1PR1) expression. Importantly, IL-22 stimuli promoted the expression of IL-22R1 and S1PR1 in aggressive MDA-MB-231 breast cancer cells. IL-22 treatment also increased sphingosine-1-phosphate production in mesenchymal stem cells (MSCs) and induced the sphingosine-1-phosphate (S1P)-mediated chemotactic migration of MDA-MB-231 cells. This effect was inhibited by an S1P antagonist. In addition to the S1PR1 axis, IL-22 stimulated the expression of matrix metalloproteinase-9 (MMP-9), thereby promoting breast cancer cell invasion. Moreover, IL-22 induced IL22R1 and S1PR1 expression in macrophages, myeloid cell, and MCP1 expression in MSCs to facilitate macrophage infiltration. Immunohistochemistry indicated that IL-22R1 and S1PR1 are overexpressed in invasive malignant breast cancers and that this correlates with the MMP-9 levels. Collectively, our present results indicate a potential role of IL-22 in driving the metastasis of breast cancers into the bone microenvironment through the IL22R1-S1PR1 axis. |
| first_indexed | 2024-03-12T10:42:38Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:42:38Z |
| publishDate | 2020-01-01 |
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| spelling | doaj.art-616077075f4844ed8e65048587393f4b2023-09-02T07:57:08ZengMDPI AGCells2073-44092020-01-019113110.3390/cells9010131cells9010131Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR SignalingEun-Young Kim0Bongkun Choi1Ji-Eun Kim2Si-On Park3Sang-Min Kim4Eun-Ju Chang5Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaThe interleukin-22 (IL-22) signaling pathway is well known to be involved in the progression of various cancer types but its role in bone metastatic breast cancer remains unclear. We demonstrate using human GEO profiling that bone metastatic breast cancer displays elevated interleukin-22 receptor 1 (IL-22R1) and sphingosine-1-phosphate receptor 1 (S1PR1) expression. Importantly, IL-22 stimuli promoted the expression of IL-22R1 and S1PR1 in aggressive MDA-MB-231 breast cancer cells. IL-22 treatment also increased sphingosine-1-phosphate production in mesenchymal stem cells (MSCs) and induced the sphingosine-1-phosphate (S1P)-mediated chemotactic migration of MDA-MB-231 cells. This effect was inhibited by an S1P antagonist. In addition to the S1PR1 axis, IL-22 stimulated the expression of matrix metalloproteinase-9 (MMP-9), thereby promoting breast cancer cell invasion. Moreover, IL-22 induced IL22R1 and S1PR1 expression in macrophages, myeloid cell, and MCP1 expression in MSCs to facilitate macrophage infiltration. Immunohistochemistry indicated that IL-22R1 and S1PR1 are overexpressed in invasive malignant breast cancers and that this correlates with the MMP-9 levels. Collectively, our present results indicate a potential role of IL-22 in driving the metastasis of breast cancers into the bone microenvironment through the IL22R1-S1PR1 axis.https://www.mdpi.com/2073-4409/9/1/131interleukin 22breast canceril22r1s1ps1pr1metastasis |
| spellingShingle | Eun-Young Kim Bongkun Choi Ji-Eun Kim Si-On Park Sang-Min Kim Eun-Ju Chang Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling Cells interleukin 22 breast cancer il22r1 s1p s1pr1 metastasis |
| title | Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling |
| title_full | Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling |
| title_fullStr | Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling |
| title_full_unstemmed | Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling |
| title_short | Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling |
| title_sort | interleukin 22 mediates the chemotactic migration of breast cancer cells and macrophage infiltration of the bone microenvironment by potentiating s1p sipr signaling |
| topic | interleukin 22 breast cancer il22r1 s1p s1pr1 metastasis |
| url | https://www.mdpi.com/2073-4409/9/1/131 |
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