[The suppressing effect of TIMP-3 gene transfection on the invasion and metastasis of human lung carcinoma cells line].
OBJECTIVE
The purpose of this study is to determine if increasing levels of tissue inhibitor of metalloproteinase 3 (TIMP-3) expression could suppress the malignant phenotype of human cancer cells.


METHODS
The recombinant expression vector, which contains full length cDNA of human TIMP-3, was constructed and transfected into BE1 cell line by lipofectin technique. The invasive and spontaneous metastatic potential was examined.


RESULTS
TIMP-3 mRNA expression in TIMP-3 gene transfected BE1 cells was upregulated as detected by Northern blot. The invasion of TIMP-3 gene-transfected cells across matrigel-coated filters was significantly decreased when compared with controls. Following subcutaneous injection into nude mice, the TIMP-3 transfected cells suppressed primary tumor growth, as characterized by reduced tumor incidence (9/12 vs 6/6), longer latency and reduced metastatic potential to the lungs (1/12 vs 5/6) and lymph nodes (5/12 vs 6/6).


CONCLUSIONS
The results suggest that upregulation of TIMP-3 expression in BE1 cells resulted in suppression of the invasive potential of BE1 cells in vitro as well as tumorigenic and metastatic potential in nude mice.
Department of Pathology, Beijing Medical University, Beijing 100083.
G
G
Niu
W
W
Fang
J
J
Zheng
D000818:Animals; D018286:Carcinoma, Giant Cell / Q000556:secondary*; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3