Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate Cancer
Background: MSCs are known to secrete abundant CCL2, which plays a crucial role in recruiting TAMs, promoting tumor progression. It is important to know whether disrupting MSC-derived CCL2 affects tumor growth. Methods: Murine bone marrow-derived MSCs were characterized by their surface markers and...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/2/441 |
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| author | Quoc Thang Bui Kuan-Der Lee Yu-Ching Fan Branwen S. Lewis Lih-Wen Deng Yuan-Chin Tsai |
| author_facet | Quoc Thang Bui Kuan-Der Lee Yu-Ching Fan Branwen S. Lewis Lih-Wen Deng Yuan-Chin Tsai |
| author_sort | Quoc Thang Bui |
| collection | DOAJ |
| description | Background: MSCs are known to secrete abundant CCL2, which plays a crucial role in recruiting TAMs, promoting tumor progression. It is important to know whether disrupting MSC-derived CCL2 affects tumor growth. Methods: Murine bone marrow-derived MSCs were characterized by their surface markers and differentiation abilities. Proliferation and migration assays were performed in order to evaluate the functions of MSCs on cancer cells. CCL2 expression in MSCs was reduced by small interfering RNA (siRNA) or completely disrupted by CRISPR/Cas9 knockout (KO) approaches. An immune-competent syngeneic murine model of prostate cancer was applied in order to assess the role of tumor cell- and MSC-derived CCL2. The tumor microenvironment was analyzed to monitor the immune profile. Results: We confirmed that tumor cell-derived CCL2 was crucial for tumor growth and MSCs migration. CCL2 KO MSCs inhibited the migration of the monocyte/macrophage but not the proliferation of tumor cells in vitro. However, the mice co-injected with tumor cells and CCL2 KO MSCs exhibited anti-tumor effects when compared with those given tumor cell alone and with control MSCs, partly due to increased infiltration of CD45<sup>+</sup>CD11b<sup>+</sup>Ly6G<sup>−</sup> mononuclear myeloid cells. Conclusions: Disruption of MSC-derived CCL2 enhances anti-tumor functions in an immune-competent syngeneic mouse model for prostate cancer. |
| first_indexed | 2024-03-09T13:17:58Z |
| format | Article |
| id | doaj.art-eb323bff13f84136a2a1566b9a0e2e76 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:17:58Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-eb323bff13f84136a2a1566b9a0e2e762023-11-30T21:33:55ZengMDPI AGCancers2072-66942023-01-0115244110.3390/cancers15020441Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate CancerQuoc Thang Bui0Kuan-Der Lee1Yu-Ching Fan2Branwen S. Lewis3Lih-Wen Deng4Yuan-Chin Tsai5International Ph.D. Program for Cell Therapy and Regeneration Medicine (IPCTRM), College of Medicine, Taipei Medical University, Taipei 110301, TaiwanInternational Ph.D. Program for Cell Therapy and Regeneration Medicine (IPCTRM), College of Medicine, Taipei Medical University, Taipei 110301, TaiwanPh.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 110301, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110301, TaiwanDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD 7, 8 Medical Drive, Singapore 117596, SingaporeGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110301, TaiwanBackground: MSCs are known to secrete abundant CCL2, which plays a crucial role in recruiting TAMs, promoting tumor progression. It is important to know whether disrupting MSC-derived CCL2 affects tumor growth. Methods: Murine bone marrow-derived MSCs were characterized by their surface markers and differentiation abilities. Proliferation and migration assays were performed in order to evaluate the functions of MSCs on cancer cells. CCL2 expression in MSCs was reduced by small interfering RNA (siRNA) or completely disrupted by CRISPR/Cas9 knockout (KO) approaches. An immune-competent syngeneic murine model of prostate cancer was applied in order to assess the role of tumor cell- and MSC-derived CCL2. The tumor microenvironment was analyzed to monitor the immune profile. Results: We confirmed that tumor cell-derived CCL2 was crucial for tumor growth and MSCs migration. CCL2 KO MSCs inhibited the migration of the monocyte/macrophage but not the proliferation of tumor cells in vitro. However, the mice co-injected with tumor cells and CCL2 KO MSCs exhibited anti-tumor effects when compared with those given tumor cell alone and with control MSCs, partly due to increased infiltration of CD45<sup>+</sup>CD11b<sup>+</sup>Ly6G<sup>−</sup> mononuclear myeloid cells. Conclusions: Disruption of MSC-derived CCL2 enhances anti-tumor functions in an immune-competent syngeneic mouse model for prostate cancer.https://www.mdpi.com/2072-6694/15/2/441CCL2mesenchymal stem cellstumor associated macrophagestumor microenvironmentCD11b<sup>+</sup>Ly6G<sup>−</sup> |
| spellingShingle | Quoc Thang Bui Kuan-Der Lee Yu-Ching Fan Branwen S. Lewis Lih-Wen Deng Yuan-Chin Tsai Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate Cancer Cancers CCL2 mesenchymal stem cells tumor associated macrophages tumor microenvironment CD11b<sup>+</sup>Ly6G<sup>−</sup> |
| title | Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate Cancer |
| title_full | Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate Cancer |
| title_fullStr | Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate Cancer |
| title_full_unstemmed | Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate Cancer |
| title_short | Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate Cancer |
| title_sort | disruption of ccl2 in mesenchymal stem cells as an anti tumor approach against prostate cancer |
| topic | CCL2 mesenchymal stem cells tumor associated macrophages tumor microenvironment CD11b<sup>+</sup>Ly6G<sup>−</sup> |
| url | https://www.mdpi.com/2072-6694/15/2/441 |
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