TIMP-2 gene transfer via adenovirus inhibits the invasion of lung cancer cell.
10.4046/trd.2000.49.2.189
- Author:
Yeon Mok OH
;
Jae Ho LEE
;
Chul Gyu YOO
;
Hee Soon CHUNG
;
Young Whan KIM
;
Sung Koo HAN
;
Young Soo SHIM
;
Choon Taek LEE
- Publication Type:In Vitro ; Original Article
- Keywords:
TIMP-2;
Gene transfer;
Lung cancer;
Invasion
- MeSH:
Adenoviridae*;
Agar;
Calcium;
Genetic Therapy;
Humans;
Lung Neoplasms*;
Lung*;
Parents;
Peptide Hydrolases;
Recombination, Genetic;
Tissue Inhibitor of Metalloproteinase-2*
- From:Tuberculosis and Respiratory Diseases
2000;49(2):189-197
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Tissue inhibitor of metalloproteinase is a natural inhibitor that counteracts proteolytic enzymes essential to the invasion of cancer cell. Whether or not TIMP-2 gene transfer via adenovirus could inhibit the invasion of lung cancer cell in vitro was evaluated for the future purpose of gene therapy against lung cancer. METHODS: Recombinant adenvirus-TIMP-2(Ad-TIMP-2) was generated by homologeous recombination after pACCMV-TIMP-2 and pJM17 were cotransfected into 293 cell by standard calcium phosphate coprecipitate mathod. Calu-6, one of the most invasive lung cancer cells, was transduced with Ad-TIMP-2 or Ad-β-gal. An-chorage-independent growth and invasiveness were assessed by soft agar clonogenicity assay and invasion assay using two-chamber, well divided by matrigel. RESULTS: Ad-TIMP-2 transduced calu-6 cells produced bilolgically active TIMP-2 more than 50 times more than parental calu-6. TIMP-2 gene transfer did not suppress the in vitro tumorgenicity. However, two chamber well assay revealed that Ad-TIMP-2 transduction reduced the invasiveness of calu-6 efficiently (12% compared with parental cell) even at low 10moi. CONCLUSION: Even though TIMP-2 gene transfer did not inhibit in vitr tumorigenicity, it did inhibit invasion of lung cancer cell in vitro. The inhibition of invasion by Ad-TIMP-2 may be a useful strategy for the treatment of lung cancer.
