ダウンロード数: 217
このアイテムのファイル:
ファイル | 記述 | サイズ | フォーマット | |
---|---|---|---|---|
cam4.886.pdf | 511.78 kB | Adobe PDF | 見る/開く |
タイトル: | CCL2 as a potential therapeutic target for clear cell renal cell carcinoma |
著者: | Arakaki, Ryuichiro Yamasaki, Toshinari Kanno, Toru Shibasaki, Noboru Sakamoto, Hiromasa Utsunomiya, Noriaki Sumiyoshi, Takayuki Shibuya, Shinsuke Tsuruyama, Tatsuaki Nakamura, Eijiro Ogawa, Osamu Kamba, Tomomi |
著者名の別形: | 山﨑, 俊成 柴崎, 昇 鶴山, 竜昭 小川, 修 神波, 大己 |
キーワード: | Angiogenesis Chemokine (C-C motif) ligand-2 Renal cell carcinoma Tumor macrophage Xenograft |
発行日: | 26-Sep-2016 |
出版者: | Wiley-Blackwell |
誌名: | Cancer Medicine |
巻: | 5 |
号: | 10 |
開始ページ: | 2920 |
終了ページ: | 2933 |
抄録: | We previously reported that the pVHL-atypical PKC-JunB pathway contributed to promotion of cell invasiveness and angiogenesis in clear cell renal cell carcinoma (ccRCC), and we detected chemokine (C-C motif) ligand-2 (CCL2) as one of downstream effectors of JunB. CCL2 plays a critical role in tumorigenesis in other types of cancer, but its role in ccRCC remains unclear. In this study, we investigated the roles and therapeutic potential of CCL2 in ccRCC. Immunohistochemical analysis of CCL2 expression for ccRCC specimens showed that upregulation of CCL2 expression correlated with clinical stage, overall survival, and macrophage infiltration. For functional analysis of CCL2 in ccRCC cells, we generated subclones of WT8 cells that overexpressed CCL2 and subclones 786-O cells in which CCL2 expression was knocked down. Although CCL2 expression did not affect cell proliferation in vitro, CCL2 overexpression enhanced and CCL2 knockdown suppressed tumor growth, angiogenesis, and macrophage infiltration in vivo. We then depleted macrophages from tumor xenografts by administration of clodronate liposomes to confirm the role of macrophages in ccRCC. Depletion of macrophages suppressed tumor growth and angiogenesis. To examine the effect of inhibiting CCL2 activity in ccRCC, we administered CCL2 neutralizing antibody to primary RCC xenografts established from patient surgical specimens. Inhibition of CCL2 activity resulted in significant suppression of tumor growth, angiogenesis, and macrophage infiltration. These results suggest that CCL2 is involved in angiogenesis and macrophage infiltration in ccRCC, and that CCL2 could be a potential therapeutic target for ccRCC. |
著作権等: | © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/217019 |
DOI(出版社版): | 10.1002/cam4.886 |
PubMed ID: | 27666332 |
出現コレクション: | 学術雑誌掲載論文等 |
このリポジトリに保管されているアイテムはすべて著作権により保護されています。