趨化素3與骨肉瘤血管新生之關係

廖芫雅

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趨化素3與骨肉瘤血管新生之關係

The Relationship Between Chemokine Ligand 3 And Angiogenesis of Osteosarcoma

廖芫雅 , Ph.D　　Advisor：周明智　　

繁體中文

MAPK ； miR-374b ； VEGF ； Angiogenesis ； Osteosarcoma ；血管新生；骨肉瘤

Abstract │ Reference (76) │ Altmetrics

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Osteosarcoma is the most common sarcoma of bone, characterized by a high metastatic potential. However, the crosstalk between chemokine (C-C motif) ligand 3 (CCL3), which facilitates tumor progression and metastasis are largely unknown. 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 expressions, quantified by immunohistochemistry, with the tumor stage of human osteosarcoma tissues. Furthermore, CCL3 promotes VEGF expression in human osteosarcoma cells that subsequently induces human endothelial progenitor cells (EPCs) migration and tube formation. Phosphorylation of JNK, ERK, and p38 was found after CCL3 stimulation. In addition, JNK, ERK, and p38 inhibitor also abolished CCL3-induced VEGF expression and angiogenesis. We noted that CCL3 reduces the expression of miR-374b and miR-374b mimic by reversing CCL3-promoted VEGF expression and angiogenesis in vitro and in vivo. This study shows that CCL3 promotes VEGF 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.

Reference ( 76 ) 〈TOP〉

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