成纤维细胞分泌TIMP-1抑制小鼠黑色素瘤细胞浸润和转移  

TIMP-1 Secreted by Fibroblasts Inhibits Tumor Cell Invasion and Metastasis in Mouse Melanoma

作　　者：沈维干[1] 朱军[1] 于智勇[2] 薛庆於[2] 

机构地区：[1]扬州大学医学院,扬州225001 [2]扬州教育学院生物系,扬州225000

出　　处：《生物医学工程学杂志》2009年第3期610-614,共5页Journal of Biomedical Engineering

基　　金：扬州大学生命科学学科群项目资助

摘　　要：构建含人金属蛋白酶-1组织抑制剂(TIMP-1)基因的重组腺病毒载体(Ad-TIMP-1)。通过Ad-TIMP-1感染原代培养的小鼠成纤维细胞,研究Ad-TIMP-1成纤维细胞对小鼠黑色素瘤细胞浸润和转移的影响。结果显示,Ad-TIMP-1原代成纤维细胞能有效表达并分泌TIMP-1;其分泌的TIMP-1可以在体内和体外显著抑制小鼠黑色素瘤B16BL6细胞的浸润和转移;皮下注射Ad-TIMP-1原代成纤维细胞制剂到小鼠体内,可以分泌TIMP-1进入小鼠血液中并维持较高水平。提示,腺病毒介导的分泌型TIMP-1原代成纤维细胞制剂可以为临床治疗肿瘤转移提供一种新的基因治疗手段,具有潜在临床应用价值。We constructed a recombinant adenoviral vector expressing human tissue inhibitors of metalloproteinase-1 （TIMP-1）, and evaluated the inhibition of TIMP-1 secreted by primary fibroblasts after infection with adenovirus-mediated TIMP-1 gene（Ad-TIMP-1） on tumor cell invasion and metastasis in mouse melanoma. It was found that TIMP-1 was dectected in the supernatants of cultured mouse primary fibroblasts after infection with Ad-TIMP- 1 by indirect enzyme-linked immunosorbent assay {ELISA）. The TIMP-1 secreted by Ad-TIMP-1 infected primary fibroblast significantly inhibited B16BL6 cell invasion and metastasis both in vitro and in vivo. We also demonstrated that the primary fibroblasts transfeeted by Ad-TIMP-1, after being subcutaneously injected into mouse~ can secreted TIMP-1 into the blood of mouse and maintained at the therapeutic in vivo levels of TIMP-1. These results suggest that the preparation of Ad-TIMP-1 infected primary fibroblast be an effective method to deliver TIMP-1 gene in vivo, which provids a new strategy of gene therapy and has the potential for clinical applications in the treatment of tumor cell metastasis

关 键 词：金属蛋白酶-1组织抑制剂 重组腺病毒 成纤维细胞 黑色素瘤 转移 

分 类 号：R739.5[医药卫生—肿瘤]