|
キタハラ シユウジ
Kitahara Shiyuuji
北原 秀治 所属 医学研究科 医学研究科 (医学部医学科をご参照ください) 職種 特任准教授 |
|
| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Vasohibin-2 modulates tumor onset in the gastrointestinal tract by normalizing tumor angiogenesis. |
| 掲載誌名 | 正式名：Molecular cancer 略 称：Mol Cancer ISSNコード：14764598/14764598 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 13,pp.99 |
| 著者・共著者 | Kitahara Shuji, Suzuki Yasuhiro, Morishima Masae, Yoshii Asuka, Kikuta Sachiko, Shimizu Kazuhiko, Morikawa Shunichi, Sato Yasufumi, Ezaki Taichi |
| 発行年月 | 2014/05 |
| 概要 | BACKGROUND:Vasohibin-2 (VASH2) has been identified as an endogenous and vascular endothelial growth factor (VEGF)-independent angiogenic factor that is highly expressed in tumor cells. In the present study, we aimed to determine whether pre-existing vascular changes can be used to predict tumor transformation as benign or malignant. We sought to characterize microvascular changes and tumor development in the intestinal tract of ApcMin/+ mice and ApcMin/+/Vash2-/- mice.METHODS:ApcMin/+ mice provide a unique orthotopic model for the development of spontaneous adenomatous polyposis and subsequent carcinomas, a phenomenon termed the adenoma-carcinoma sequence. ApcMin/+ mice were mated with Vash2-/- mice with a mixed C57BL/6 background and the resulting pups were screened for the Min mutation and for the Vash2-/- gene by PCR. Intestinal tumors from ApcMin/+ mice and ApcMin/+/Vash2-/- mice were removed and either frozen or epon-embedded for subsequent analyses. For 3-dimensional imaging using confocal laser-scanning microscopy and transmission electron microscopy, cryosections were made, and immunofluorescent staining for various markers was performed.RESULTS:We found that structural abnormalities in tumor vessels from benign tumors resembled those in malignant tumors. In addition, a novel angiogenic factor, vasohibin-2 (VASH2) protein, was detected around tumor blood vessels in late-stage adenomas and adenocarcinomas, but was absent from early-stage adenomas in ApcMin/+ mice. Tumors used to examine endogenous VASH2 (derived from CMT93 colon carcinomas) were less vascularized in Vash2-/- mice and were more regular than those seen in wild-type (WT) mice. In addition, tumors in Vash2-/- mice were smaller than those in WT mice. Furthermore, cross-breeding of mice homozygous for a deletion of Vash2 with mice heterozygous for the APC mutation resulted in animals that showed a significant decrease in the number of polyps in the small intestine.CONCLUSION:We propose that VASH2 m |
| DOI | 10.1186/1476-4598-13-99 |
| PMID | 24885408 |