Studies of endothelin-1 in metastasis of human chondrosarcoma
| Autor: | Min-Huan Wu, 吳旻寰 |
|---|---|
| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Chondrosarcoma is a type of highly malignant tumor with a potent capacity of local invasion and distant metastasis. Cell migration and angiogenesis is essential for the caner metastasis. Endothelin-1 (ET-1) has been implicated in tumor angiogenesis and metastasis. However, the effect of ET-1 on metastasis and angiogenesis activity in human chondrosarcoma cells is not clearly understood. Here, we found that ET-1 increased the migration, angiogenesis and expression of matrix metalloproteinase (MMP)-13, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF) in human chondrosarcoma cells. Human chondrosarcoma tissues had significant expression levels of ET-1, COX-2, and VEGF which significantly higher than those in normal cartilage. Aberrant ET-1 increased cell migration and the expression of MMP-13 and COX-2. In addition, MMP-13 and COX-2 expression as well as cell migration ability were abolished by ET receptor antagonists. Exogenous ET-1 with chondrosarcoma cells promoted VEGF expression and subsequently increased migration and tube formation in endothelial progenitor cells. Furthermore, knockdown of ET-1 decreased cell metastasis also abolished chondrosarcoma conditional medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and matrigel-plug nude mice model in vivo. In addition, using xenograft tumor model, knockdown ET-1 significantly reduced tumor growth and tumor-associated angiogenesis. Taken together, these results suggest that ET-1 increased MMP-13, COX-2, and VEGF expression and contributing the tumor growth, angiogenesis, and metastasis of human chondrosarcoma cells. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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