論文 - 詳細
| RRC ID | 18898 |
|---|---|
| 著者 | Tsuchiya K, Hida K, Hida Y, Muraki C, Ohga N, Akino T, Kondo T, Miseki T, Nakagawa K, Shindoh M, Harabayashi T, Shinohara N, Nonomura K, Kobayashi M. |
| タイトル | Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through inhibitory effects on tumor endothelial cells and endothelial progenitor mobilization. |
| ジャーナル | Int J Oncol |
| Abstract |
Adrenomedullin (AM) is a multifunctional 52-amino acid peptide. AM has several effects and acts as a growth factor in several types of cancer cells. Our previous study revealed that an AM antagonist (AMA) suppressed the growth of pancreatic tumors in mice, although its mechanism was not elucidated. In this study, we constructed an AMA expression vector and used it to treat renal cell carcinoma (RCC) in mice. This AMA expression vector significantly reduced tumor growth in mice. In addition, microvessel density was decreased in AMA-treated tumors. To analyze the effect of AMA on tumor angiogenesis in this model, tumor endothelial cells (TECs) were isolated from RCC xenografts. TEC proliferation was stimulated by AM and it was inhibited by AMA significantly. AM induced migration of TECs and it was also blocked by AMA. However, normal ECs (NECs) were not affected by either AM or AMA. These results demonstrate that AMA has inhibitory effects on TECs specifically, not on NEC, thereby inhibiting tumor angiogenesis. Furthermore, we showed that vascular endothelial growth factor-induced mobilization of endothelial progenitor cell (EPC) into circulation was inhibited by AMA. These results suggest that AMA can be considered a good anti-angiogenic reagent that selectively targets TECs and EPC in renal cancer. |
| 巻・号 | 36(6) |
| ページ | 1379-86 |
| 公開日 | 2010-6-1 |
| DOI | 10.3892/ijo_00000622 |
| PMID | 20428760 |
| MeSH | Adrenomedullin / antagonists & inhibitors* Animals Antineoplastic Agents / therapeutic use* Carcinoma, Renal Cell / blood supply Carcinoma, Renal Cell / therapy* Cell Line, Tumor Cell Proliferation DNA / therapeutic use* Endothelial Cells / metabolism Endothelial Cells / pathology Female Genetic Therapy / methods* Humans Immunohistochemistry Kidney Neoplasms / blood supply Kidney Neoplasms / therapy* Mice Mice, Nude Neovascularization, Pathologic / therapy Reverse Transcriptase Polymerase Chain Reaction Stem Cells / cytology Stem Cells / metabolism Xenograft Model Antitumor Assays |
| IF | 3.899 |
| 引用数 | 34 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | OS-RC-2(RCB0735) |