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CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells

Osteosarcoma is the most frequent bone tumor, characterized by a high metastatic potential. However, the crosstalk between chemokine (C-C motif) ligand 3 (CCL3), which facilitates tumor progression and metastasis. Vascular endothelial growth factor-A (VEGF-A), an angiogenesis inducer and a highly sp...

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Autores principales: Liao, Yuan-Ya, Tsai, Hsiao-Chi, Chou, Pei-Yu, Wang, Shih-Wei, Chen, Hsien-Te, Lin, Yu-Min, Chiang, I-Ping, Chang, Tzu-Ming, Hsu, Shao-Keh, Chou, Ming-Chih, Tang, Chih-Hsin, Fong, Yi-Chin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826207/
https://www.ncbi.nlm.nih.gov/pubmed/26713602
http://dx.doi.org/10.18632/oncotarget.6708
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author Liao, Yuan-Ya
Tsai, Hsiao-Chi
Chou, Pei-Yu
Wang, Shih-Wei
Chen, Hsien-Te
Lin, Yu-Min
Chiang, I-Ping
Chang, Tzu-Ming
Hsu, Shao-Keh
Chou, Ming-Chih
Tang, Chih-Hsin
Fong, Yi-Chin
author_facet Liao, Yuan-Ya
Tsai, Hsiao-Chi
Chou, Pei-Yu
Wang, Shih-Wei
Chen, Hsien-Te
Lin, Yu-Min
Chiang, I-Ping
Chang, Tzu-Ming
Hsu, Shao-Keh
Chou, Ming-Chih
Tang, Chih-Hsin
Fong, Yi-Chin
author_sort Liao, Yuan-Ya
collection PubMed
description Osteosarcoma is the most frequent bone tumor, characterized by a high metastatic potential. However, the crosstalk between chemokine (C-C motif) ligand 3 (CCL3), which facilitates tumor progression and metastasis. Vascular endothelial growth factor-A (VEGF-A), an angiogenesis inducer and a highly specific mitogen for endothelial cells, has not been well explored in human osteosarcoma. Here we demonstrate the correlation of CCL3 and VEGF-A expressions, quantified by immunohistochemistry, with the tumor stage of human osteosarcoma tissues. Furthermore, CCL3 promotes VEGF-A expression in human osteosarcoma cells that subsequently induces human endothelial progenitor cell (EPC) migration and tube formation. Phosphorylation of JNK, ERK, and p38 was found after CCL3 stimulation. In addition, JNK, ERK, and p38 inhibitors also abolished CCL3-induced VEGF-A expression and angiogenesis. We noted that CCL3 reduces the expression of miR-374b and miR-374b mimic by reversing CCL3-promoted VEGF-A expression and angiogenesis in vitro and in vivo. This study shows that CCL3 promotes VEGF-A expression and angiogenesis in human osteosarcoma cells by down-regulating miR-374b expression via JNK, ERK, and p38 signaling pathways. Thus, CCL3 may be a new molecular therapeutic target in osteosarcoma angiogenesis and metastasis.
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spelling pubmed-48262072016-05-09 CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells Liao, Yuan-Ya Tsai, Hsiao-Chi Chou, Pei-Yu Wang, Shih-Wei Chen, Hsien-Te Lin, Yu-Min Chiang, I-Ping Chang, Tzu-Ming Hsu, Shao-Keh Chou, Ming-Chih Tang, Chih-Hsin Fong, Yi-Chin Oncotarget Research Paper Osteosarcoma is the most frequent bone tumor, characterized by a high metastatic potential. However, the crosstalk between chemokine (C-C motif) ligand 3 (CCL3), which facilitates tumor progression and metastasis. Vascular endothelial growth factor-A (VEGF-A), an angiogenesis inducer and a highly specific mitogen for endothelial cells, has not been well explored in human osteosarcoma. Here we demonstrate the correlation of CCL3 and VEGF-A expressions, quantified by immunohistochemistry, with the tumor stage of human osteosarcoma tissues. Furthermore, CCL3 promotes VEGF-A expression in human osteosarcoma cells that subsequently induces human endothelial progenitor cell (EPC) migration and tube formation. Phosphorylation of JNK, ERK, and p38 was found after CCL3 stimulation. In addition, JNK, ERK, and p38 inhibitors also abolished CCL3-induced VEGF-A expression and angiogenesis. We noted that CCL3 reduces the expression of miR-374b and miR-374b mimic by reversing CCL3-promoted VEGF-A expression and angiogenesis in vitro and in vivo. This study shows that CCL3 promotes VEGF-A expression and angiogenesis in human osteosarcoma cells by down-regulating miR-374b expression via JNK, ERK, and p38 signaling pathways. Thus, CCL3 may be a new molecular therapeutic target in osteosarcoma angiogenesis and metastasis. Impact Journals LLC 2015-12-21 /pmc/articles/PMC4826207/ /pubmed/26713602 http://dx.doi.org/10.18632/oncotarget.6708 Text en Copyright: © 2016 Liao et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liao, Yuan-Ya
Tsai, Hsiao-Chi
Chou, Pei-Yu
Wang, Shih-Wei
Chen, Hsien-Te
Lin, Yu-Min
Chiang, I-Ping
Chang, Tzu-Ming
Hsu, Shao-Keh
Chou, Ming-Chih
Tang, Chih-Hsin
Fong, Yi-Chin
CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells
title CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells
title_full CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells
title_fullStr CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells
title_full_unstemmed CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells
title_short CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells
title_sort ccl3 promotes angiogenesis by dysregulation of mir-374b/ vegf-a axis in human osteosarcoma cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826207/
https://www.ncbi.nlm.nih.gov/pubmed/26713602
http://dx.doi.org/10.18632/oncotarget.6708
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