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イタノ ナオキ
ITANO NAOKI
板野 直樹 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2010/09 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization |
| 執筆形態 | その他 |
| 掲載誌名 | CANCER RESEARCH |
| 出版社・発行元 | AMER ASSOC CANCER RESEARCH |
| 巻・号・頁 | 70(18),pp.7073-7083 |
| 著者・共著者 | Nobutaka Kobayashi,Seiji Miyoshi,Takahide Mikami,Hiroshi Koyama,Masato Kitazawa,Michiko Takeoka,Kenji Sano,Jun Amano,Zenzo Isogai,Shumpei Niida,Kayoko Oguri,Minoru Okayama,John A. McDonald,Koji Kimata,Shun'ichiro Taniguchi,Naoki Itano |
| 概要 | Despite the importance of stromal cells in tumor progression, our overall understanding of the molecular signals that regulate the complex cellular interactions within tumor stroma is limited. Here, we provide multiple lines of evidence that tumor-associated macrophages (TAM) preferentially traffic to stromal areas formed within tumors in a manner dependent on a hyaluronan (HA)-rich tumor microenvironment. To address the role of stroma-derived HA in macrophage recruitment, we disrupted the HA synthase 2 (Has2) gene in stromal fibroblasts using conditional gene targeting. The Has2 null fibroblasts showed severe impairment in recruiting macrophages when inoculated with tumor cells into nude mice, which shows the contribution of stroma-derived HA in intratumoral macrophage mobilization. Furthermore, a deficiency in stromal HA attenuated tumor angiogenesis and lymphangiogenesis concomitantly with impaired macrophage recruitment. Taken together, our results suggest that stromal HA serves as a microenvironmental signal for the recruitment of TAMs, which are key regulatory cells involved in tumor neovascularization. Cancer Res; 70(18); 7073-83. (C)2010 AACR. |
| DOI | 10.1158/0008-5472.CAN-09-4687 |
| ISSN | 0008-5472 |