TIMP-1 secreted by fibroblasts inhibits tumor cell invasion and metastasis in mouse melanoma.
- Author:
Weigan SHEN
1
;
Jun ZHU
;
Zhiyong YU
;
Qingyu XUE
Author Information
1. Medical College of Yangzhou University, Yangzhou 225001, China. weiganshen@yahoo.com.cn
- Publication Type:Journal Article
- MeSH:
Adenoviridae;
genetics;
metabolism;
Animals;
Female;
Fibroblasts;
metabolism;
Genetic Therapy;
Humans;
Melanoma, Experimental;
pathology;
therapy;
Mice;
Mice, Inbred C57BL;
Neoplasm Invasiveness;
Neoplasm Metastasis;
Recombinant Proteins;
biosynthesis;
genetics;
pharmacology;
Tissue Inhibitor of Metalloproteinase-1;
biosynthesis;
genetics;
pharmacology
- From:
Journal of Biomedical Engineering
2009;26(3):610-614
- CountryChina
- Language:Chinese
-
Abstract:
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 detected 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 transfected 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 provides a new strategy of gene therapy and has the potential for clinical applications in the treatment of tumor cell metastasis.
