https://scholars.lib.ntu.edu.tw/handle/123456789/595796
標題: | Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway | 作者: | Chien, Ming-Hsien CHIA-CHI KU Johansson, Gunnar Chen, Min-Wei Hsiao, Michael Su, Jen-Liang Inoue, Hiroyasu Hua, Kuo-Tai LING-HUNG WEI Kuo, Min-Liang |
關鍵字: | ACUTE MYELOID-LEUKEMIA; CAMP-RESPONSE ELEMENT; CYCLOOXYGENASE-2 EXPRESSION; CANCER-CELLS; RECEPTOR VEGFR-3; VEGF-C/VEGFR-3 AXIS; TUMOR ANGIOGENESIS; LYMPHATIC VESSELS; FACTOR (VEGF)-C; JNK PATHWAYS | 公開日期: | 十二月-2009 | 出版社: | OXFORD UNIV PRESS | 卷: | 30 | 期: | 12 | 起(迄)頁: | 2005 | 來源出版物: | Carcinogenesis | 摘要: | Vascular endothelial growth factor (VEGF)-C is recognized as a tumor lymphangiogenic factor based on the effects of activated VEGF-R3 on lymphatic endothelial cells. Many tumor cells express VEGF-R3 but the function of this receptor in tumor cells is largely unknown. It has been reported that the VEGF-C/VEGF-R3 axis is activated in subsets of leukemia patients. Herein, we have shown that VEGF-C induces angiogenic activity in the tube formation assay invitro and Matrigel plug assay in vivo by upregulating an angiogenic factor, cyclooxygenase-2 (COX-2), through VEGF-R3 in the human acute myeloid leukemia (AML) cell line, THP-1. COX-2 induction by VEGF-C was also observed in other VEGF-R3(+) human AML cell lines (U937 and HL60). Moreover, immunohistochemical analysis of bone marrow specimens of 37 patients diagnosed with AML revealed that VEGF-C expression in specimens was associated with the expression of COX-2 (P < 0.001). The manner by which signaling pathways transduced by VEGF-C is responsible for COX-2 upregulation was further investigated. Blocking the p42/44 mitogen-activated protein kinase (MAPK) pathway with the MAPK kinase inhibitor, PD 98059, failed to inhibit VEGF-C-mediated COX-2 expression. However, VEGF-C-induced COX-2 upregulation was effectively abolished by overexpression of dominant-negative c-Jun N-terminal kinase (JNK) or treatment with the JNK inhibitor, SP 600125. VEGF-C induced JNK-dependent nuclear translocation of c-Jun. Furthermore, chromatin immunoprecipitation and reporter assays revealed that VEGF-C enhanced c-Jun binding to the cyclic adenosine 3',5'-monophosphate-response element of the COX-2 promoter and induced COX-2 expression. In sum, the data herein highlight the pathogenic role of VEGF-C in leukemia via regulation of angiogenesis through upregulation of COX-2. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/595796 | ISSN: | 1460-2180 0143-3334 |
DOI: | 10.1093/carcin/bgp244 |
顯示於: | 免疫學研究所 |
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