[Effects of TIMP-2 gene transfection on biological behaviors of a metastatic human lung carcinoma cell line].
OBJECTIVE
To explore the suppressive effects of tissue inhibitor of metalloproteinase 2 (TIMP-2) on malignant phenotype of human carcinoma cells and to evaluate its potential application in cancer gene therapy.


METHODS
A man malian expression vector containing TIMP-2 cDNA was constructed and transfected into a metastatic human lung carcinoma cell line PG. In vitro and in vivo tests such as Northern blotting, immunohistochemistry as well as x enografting in nude mice experiment were used to analyse expression levels of TIMPs and MMPs, in vitro and in vivo behaviors of the tumor cells before and after the gene transfection.


RESULTS
After transfection, the TIMP-2 mRNA expression was upregulated significantly. Changes, in some malignant phenotypes of the transfectants were seen. For instance, the abilities of in vitro invasion through Matrigel, colony formation on soft agar, tumorigenecity as well as spontaneous metastasis in nude mice were remarkably decreased. Immunohistochemical staining and in situ hybrydization showed that MMP2, MMP9, TIMP-1 and TIMP-2 were expressed by both tumor cells and stromal cells, with stronger staining at the site of tumor invasion.


CONCLUSIONS
Up-regulation of TIMP-2 in tumor cells could suppress their expression of malignant phenotype and could be used for cancer therapy.
Department of Pathology, Beijing Medical University.
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Li
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Fang
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Shi
D000818:Animals; D000970:Antineoplastic Agents; D018286:Carcinoma, Giant Cell / Q000235:genetics / Q000556:secondary; D017364:Collagenases / Q000096:biosynthesis; D018093:Gelatinases / Q000096:biosynthesis; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010641:Phenotype; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9