Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages
Visfatin, an adipocytokine highly expressed in breast tumor tissues, is associated with breast cancer progression. Recent studies showed that adipocytokines mediate tumor development through adipocytokine tumor-stromal interactions in the tumor microenvironment. This study focused on the interaction...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/12/3526 |
| _version_ | 1797546730067066880 |
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| author | Yen-Yun Wang Huan-Da Chen Steven Lo Yuk-Kwan Chen Yu-Ci Huang Stephen Chu-Sung Hu Ya-Ching Hsieh Amos C. Hung Ming-Feng Hou Shyng-Shiou F. Yuan |
| author_facet | Yen-Yun Wang Huan-Da Chen Steven Lo Yuk-Kwan Chen Yu-Ci Huang Stephen Chu-Sung Hu Ya-Ching Hsieh Amos C. Hung Ming-Feng Hou Shyng-Shiou F. Yuan |
| author_sort | Yen-Yun Wang |
| collection | DOAJ |
| description | Visfatin, an adipocytokine highly expressed in breast tumor tissues, is associated with breast cancer progression. Recent studies showed that adipocytokines mediate tumor development through adipocytokine tumor-stromal interactions in the tumor microenvironment. This study focused on the interaction between one key stromal constituent—tumor-associated macrophages—and visfatin. Pretreatment of THP-1 and peripheral blood mononuclear cells (PBMCs) with recombinant visfatin resulted in M2-polarization determined by CD163 and CD206 expression. Indirect co-culture with visfatin-treated THP-1 (V-THP-1) promoted the viability, migration, tumorsphere formation, EMT, and stemness of breast cancer cells. Cytokine array identified an increased CXCL1 secretion in V-THP-1 conditioned medium and recombinant CXCL1 enhanced cell migration and invasion, which were abrogated by the CXCL1-neutralizing antibody. Additionally, visfatin induced pERK in THP-1 cells and clinical samples confirmed a positive CXCL1/pERK correlation. In an orthotopic mouse model, the tumor bioluminescent signal of luciferase-expressing MDA-MB-231 (Luc-MDA-MB-231) cells co-cultured with V-THP-1 and the expression of proliferation marker Ki67 were significantly higher than that co-cultured with THP-1. Furthermore, tail vein-injected Luc-MDA-MB-231 pretreated with V-PBMCs conditioned medium metastasized to lungs more frequently compared to control, and this was reversed by CXCL1 blocking antibody. In summary, this study demonstrated that visfatin enhanced breast cancer progression via pERK/CXCL1 induction in macrophages. |
| first_indexed | 2024-03-10T14:33:22Z |
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| id | doaj.art-ccc11f0e18524ede96e144fc6b2ea936 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T14:33:22Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ccc11f0e18524ede96e144fc6b2ea9362023-11-20T22:25:28ZengMDPI AGCancers2072-66942020-11-011212352610.3390/cancers12123526Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated MacrophagesYen-Yun Wang0Huan-Da Chen1Steven Lo2Yuk-Kwan Chen3Yu-Ci Huang4Stephen Chu-Sung Hu5Ya-Ching Hsieh6Amos C. Hung7Ming-Feng Hou8Shyng-Shiou F. Yuan9School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanTranslational Research Center, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanCanniesburn Regional Plastic Surgery and Burns Unit, Glasgow Royal Infirmary, Glasgow G4 0SF, UKSchool of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanInstitute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UKTranslational Research Center, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDivision of General and Gastroenterological Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanTranslational Research Center, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanVisfatin, an adipocytokine highly expressed in breast tumor tissues, is associated with breast cancer progression. Recent studies showed that adipocytokines mediate tumor development through adipocytokine tumor-stromal interactions in the tumor microenvironment. This study focused on the interaction between one key stromal constituent—tumor-associated macrophages—and visfatin. Pretreatment of THP-1 and peripheral blood mononuclear cells (PBMCs) with recombinant visfatin resulted in M2-polarization determined by CD163 and CD206 expression. Indirect co-culture with visfatin-treated THP-1 (V-THP-1) promoted the viability, migration, tumorsphere formation, EMT, and stemness of breast cancer cells. Cytokine array identified an increased CXCL1 secretion in V-THP-1 conditioned medium and recombinant CXCL1 enhanced cell migration and invasion, which were abrogated by the CXCL1-neutralizing antibody. Additionally, visfatin induced pERK in THP-1 cells and clinical samples confirmed a positive CXCL1/pERK correlation. In an orthotopic mouse model, the tumor bioluminescent signal of luciferase-expressing MDA-MB-231 (Luc-MDA-MB-231) cells co-cultured with V-THP-1 and the expression of proliferation marker Ki67 were significantly higher than that co-cultured with THP-1. Furthermore, tail vein-injected Luc-MDA-MB-231 pretreated with V-PBMCs conditioned medium metastasized to lungs more frequently compared to control, and this was reversed by CXCL1 blocking antibody. In summary, this study demonstrated that visfatin enhanced breast cancer progression via pERK/CXCL1 induction in macrophages.https://www.mdpi.com/2072-6694/12/12/3526visfatinbreast cancertumor-associated macrophagesCXCL1 |
| spellingShingle | Yen-Yun Wang Huan-Da Chen Steven Lo Yuk-Kwan Chen Yu-Ci Huang Stephen Chu-Sung Hu Ya-Ching Hsieh Amos C. Hung Ming-Feng Hou Shyng-Shiou F. Yuan Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages Cancers visfatin breast cancer tumor-associated macrophages CXCL1 |
| title | Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages |
| title_full | Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages |
| title_fullStr | Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages |
| title_full_unstemmed | Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages |
| title_short | Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages |
| title_sort | visfatin enhances breast cancer progression through cxcl1 induction in tumor associated macrophages |
| topic | visfatin breast cancer tumor-associated macrophages CXCL1 |
| url | https://www.mdpi.com/2072-6694/12/12/3526 |
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