Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3
Microcystin-LR (MC-LR) is a toxic secondary metabolite produced by cyanobacteria that has been demonstrated to promote colorectal cancer (CRC). However, the mechanism by which MC-LR enhances CRC in the tumor microenvironment (TME) is poorly understood. To elucidate its role in TME, a co-culture syst...
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10527 |
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| author | Xinying Jiang Hailing Zhang Hengshuo Zhang Fan Wang Xiaochang Wang Tong Ding Xuxiang Zhang Ting Wang |
| author_facet | Xinying Jiang Hailing Zhang Hengshuo Zhang Fan Wang Xiaochang Wang Tong Ding Xuxiang Zhang Ting Wang |
| author_sort | Xinying Jiang |
| collection | DOAJ |
| description | Microcystin-LR (MC-LR) is a toxic secondary metabolite produced by cyanobacteria that has been demonstrated to promote colorectal cancer (CRC). However, the mechanism by which MC-LR enhances CRC in the tumor microenvironment (TME) is poorly understood. To elucidate its role in TME, a co-culture system was established using CRC cells and M2 macrophages in a Transwell chamber. The study found that MC-LR promotes CRC cell migration by upregulating TGF-β1 expression and secretion in M2 macrophages and downregulating CST3 in CRC cells. Neutralizing TGF-β1 increased CST3 expression in CRC cells, while overexpressing CST3 in CRC cells suppressed TGF-β1 expression in M2 macrophages, both of which weakened MC-LR-induced cellular motility in the co-culture system. In vivo, the mice in the MC-LR/AOM/DSS group had more tumor nodules, deeper tumor invasion, and higher M2 macrophage infiltration compared to the AOM/DSS group, and the expression of TGF-β1 and CST3 in tumors was consistent with the cellular level. Overall, this study provides insights into the regulatory mechanism of MC-LR on TME, revealing that MC-LR upregulates the expression and secretion of TGF-β1 in M2 macrophages, which in turn inhibits the expression of CST3 in CRC cells to promote migration. |
| first_indexed | 2024-03-11T01:40:12Z |
| format | Article |
| id | doaj.art-92bffd9bf5be4de391a6f2e18b97bba6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:40:12Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-92bffd9bf5be4de391a6f2e18b97bba62023-11-18T16:39:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131052710.3390/ijms241310527Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3Xinying Jiang0Hailing Zhang1Hengshuo Zhang2Fan Wang3Xiaochang Wang4Tong Ding5Xuxiang Zhang6Ting Wang7Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Xianlin Campus, Nanjing University, Nanjing 210023, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, ChinaMicrocystin-LR (MC-LR) is a toxic secondary metabolite produced by cyanobacteria that has been demonstrated to promote colorectal cancer (CRC). However, the mechanism by which MC-LR enhances CRC in the tumor microenvironment (TME) is poorly understood. To elucidate its role in TME, a co-culture system was established using CRC cells and M2 macrophages in a Transwell chamber. The study found that MC-LR promotes CRC cell migration by upregulating TGF-β1 expression and secretion in M2 macrophages and downregulating CST3 in CRC cells. Neutralizing TGF-β1 increased CST3 expression in CRC cells, while overexpressing CST3 in CRC cells suppressed TGF-β1 expression in M2 macrophages, both of which weakened MC-LR-induced cellular motility in the co-culture system. In vivo, the mice in the MC-LR/AOM/DSS group had more tumor nodules, deeper tumor invasion, and higher M2 macrophage infiltration compared to the AOM/DSS group, and the expression of TGF-β1 and CST3 in tumors was consistent with the cellular level. Overall, this study provides insights into the regulatory mechanism of MC-LR on TME, revealing that MC-LR upregulates the expression and secretion of TGF-β1 in M2 macrophages, which in turn inhibits the expression of CST3 in CRC cells to promote migration.https://www.mdpi.com/1422-0067/24/13/10527MC-LRTGF-β1M2 tumor-associated macrophagesmigrationcolorectal cancer |
| spellingShingle | Xinying Jiang Hailing Zhang Hengshuo Zhang Fan Wang Xiaochang Wang Tong Ding Xuxiang Zhang Ting Wang Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3 International Journal of Molecular Sciences MC-LR TGF-β1 M2 tumor-associated macrophages migration colorectal cancer |
| title | Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3 |
| title_full | Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3 |
| title_fullStr | Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3 |
| title_full_unstemmed | Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3 |
| title_short | Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3 |
| title_sort | microcystin lr induced interaction between m2 tumor associated macrophage and colorectal cancer cell promotes colorectal cancer cell migration through regulating the expression of tgf β1 and cst3 |
| topic | MC-LR TGF-β1 M2 tumor-associated macrophages migration colorectal cancer |
| url | https://www.mdpi.com/1422-0067/24/13/10527 |
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