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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...

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Autores principales: Chang, Yu-Hsiang, Huang, Yuan-Li, Tsai, Hsiao-Chi, Chang, An-Chen, Ko, Chih-Yuan, Fong, Yi-Chin, Tang, Chih-Hsin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604484/
https://www.ncbi.nlm.nih.gov/pubmed/37893141
http://dx.doi.org/10.3390/biomedicines11102768
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author Chang, Yu-Hsiang
Huang, Yuan-Li
Tsai, Hsiao-Chi
Chang, An-Chen
Ko, Chih-Yuan
Fong, Yi-Chin
Tang, Chih-Hsin
author_facet Chang, Yu-Hsiang
Huang, Yuan-Li
Tsai, Hsiao-Chi
Chang, An-Chen
Ko, Chih-Yuan
Fong, Yi-Chin
Tang, Chih-Hsin
author_sort Chang, Yu-Hsiang
collection PubMed
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.
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spelling pubmed-106044842023-10-28 Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis Chang, Yu-Hsiang Huang, Yuan-Li Tsai, Hsiao-Chi Chang, An-Chen Ko, Chih-Yuan Fong, Yi-Chin Tang, Chih-Hsin Biomedicines Article 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. MDPI 2023-10-12 /pmc/articles/PMC10604484/ /pubmed/37893141 http://dx.doi.org/10.3390/biomedicines11102768 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Yu-Hsiang
Huang, Yuan-Li
Tsai, Hsiao-Chi
Chang, An-Chen
Ko, Chih-Yuan
Fong, Yi-Chin
Tang, Chih-Hsin
Chemokine Ligand 2 Promotes Migration in Osteosarcoma by Regulating the miR-3659/MMP-3 Axis
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604484/
https://www.ncbi.nlm.nih.gov/pubmed/37893141
http://dx.doi.org/10.3390/biomedicines11102768
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