[TIMP-1 secreted by fibroblasts inhibits tumor cell invasion and metastasis in mouse melanoma].
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.
Shen
Weigan
W
Medical College of Yangzhou University, Yangzhou 225001, China. weiganshen@yahoo.com.cn
Zhu
Jun
J
Yu
Zhiyong
Z
Xue
Qingyu
Q
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D015316:Genetic Therapy; D006801:Humans; D008546:Melanoma, Experimental / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*
D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1