Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis
Osteosarcoma is a common malignant tumor in children and adolescents, known for its aggressive invasion and distant metastasis, leading to a poor prognosis. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basement membranes through their proteolytic activity, thereby promot...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/10/2768 |
| _version_ | 1797574621822713856 |
|---|---|
| author | Yu-Hsiang Chang Yuan-Li Huang Hsiao-Chi Tsai An-Chen Chang Chih-Yuan Ko Yi-Chin Fong Chih-Hsin Tang |
| author_facet | Yu-Hsiang Chang Yuan-Li Huang Hsiao-Chi Tsai An-Chen Chang Chih-Yuan Ko Yi-Chin Fong Chih-Hsin Tang |
| author_sort | Yu-Hsiang Chang |
| collection | DOAJ |
| description | Osteosarcoma is a common malignant tumor in children and adolescents, known for its aggressive invasion and distant metastasis, leading to a poor prognosis. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basement membranes through their proteolytic activity, thereby promoting osteosarcoma metastasis. Chemokine ligand 2 (CCL2) is a well-studied chemokine that plays a significant role in the cell motility of many cancers. However, its specific involvement in osteosarcoma metastasis is not fully understood. The aim of this study is to examine the role of miRNAs in CCL2-mediated MMP expression and cell motility in human osteosarcoma. The analysis of immunohistochemistry data and databases associated a positive correlation between CCL2 or MMP-3 levels with the metastasis of osteosarcoma patients. The in vivo lung metastatic osteosarcoma model also demonstrated similar effects, showing higher levels of CCL2 and MMP-3 in lung metastatic osteosarcoma tissues. The stimulation of osteosarcoma cells with CCL2 enhanced migration and invasion abilities through the upregulation of MMP-3 synthesis. Our results also indicate that CCL2 enhances MMP-3-dependent cell motility by inhibiting miR-3659 synthesis. Therefore, CCL2 represents a promising therapeutic target for treating metastasis in osteosarcoma. |
| first_indexed | 2024-03-10T21:24:55Z |
| format | Article |
| id | doaj.art-df841b39091645f3879556f4fb4396dc |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T21:24:55Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-df841b39091645f3879556f4fb4396dc2023-11-19T15:46:49ZengMDPI AGBiomedicines2227-90592023-10-011110276810.3390/biomedicines11102768Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 AxisYu-Hsiang Chang0Yuan-Li Huang1Hsiao-Chi Tsai2An-Chen Chang3Chih-Yuan Ko4Yi-Chin Fong5Chih-Hsin Tang6Program for Cancer Biology and Drug Discovery, China Medical University, Taichung 404328, TaiwanDepartment of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, TaiwanDepartment of Medical Education and Research, China Medical University Beigang Hospital, Yunlin 651012, TaiwanTranslational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111045, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 404328, TaiwanDepartment of Orthopedic Surgery, China Medical University Hospital, Taichung 404327, TaiwanProgram for Cancer Biology and Drug Discovery, China Medical University, Taichung 404328, TaiwanOsteosarcoma is a common malignant tumor in children and adolescents, known for its aggressive invasion and distant metastasis, leading to a poor prognosis. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basement membranes through their proteolytic activity, thereby promoting osteosarcoma metastasis. Chemokine ligand 2 (CCL2) is a well-studied chemokine that plays a significant role in the cell motility of many cancers. However, its specific involvement in osteosarcoma metastasis is not fully understood. The aim of this study is to examine the role of miRNAs in CCL2-mediated MMP expression and cell motility in human osteosarcoma. The analysis of immunohistochemistry data and databases associated a positive correlation between CCL2 or MMP-3 levels with the metastasis of osteosarcoma patients. The in vivo lung metastatic osteosarcoma model also demonstrated similar effects, showing higher levels of CCL2 and MMP-3 in lung metastatic osteosarcoma tissues. The stimulation of osteosarcoma cells with CCL2 enhanced migration and invasion abilities through the upregulation of MMP-3 synthesis. Our results also indicate that CCL2 enhances MMP-3-dependent cell motility by inhibiting miR-3659 synthesis. Therefore, CCL2 represents a promising therapeutic target for treating metastasis in osteosarcoma.https://www.mdpi.com/2227-9059/11/10/2768osteosarcomaCCL2MMP-3metastasismiR-3659 |
| spellingShingle | Yu-Hsiang Chang Yuan-Li Huang Hsiao-Chi Tsai An-Chen Chang Chih-Yuan Ko Yi-Chin Fong Chih-Hsin Tang Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis Biomedicines osteosarcoma CCL2 MMP-3 metastasis miR-3659 |
| title | Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis |
| title_full | Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis |
| title_fullStr | Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis |
| title_full_unstemmed | Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis |
| title_short | Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis |
| title_sort | chemokine ligand 2 promotes migration in osteosarcoma by regulating the mir 3659 mmp 3 axis |
| topic | osteosarcoma CCL2 MMP-3 metastasis miR-3659 |
| url | https://www.mdpi.com/2227-9059/11/10/2768 |
| work_keys_str_mv | AT yuhsiangchang chemokineligand2promotesmigrationinosteosarcomabyregulatingthemir3659mmp3axis AT yuanlihuang chemokineligand2promotesmigrationinosteosarcomabyregulatingthemir3659mmp3axis AT hsiaochitsai chemokineligand2promotesmigrationinosteosarcomabyregulatingthemir3659mmp3axis AT anchenchang chemokineligand2promotesmigrationinosteosarcomabyregulatingthemir3659mmp3axis AT chihyuanko chemokineligand2promotesmigrationinosteosarcomabyregulatingthemir3659mmp3axis AT yichinfong chemokineligand2promotesmigrationinosteosarcomabyregulatingthemir3659mmp3axis AT chihhsintang chemokineligand2promotesmigrationinosteosarcomabyregulatingthemir3659mmp3axis |