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Adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinases-3 inhibits invasion and induces apoptosis in melanoma cells
Author(s): Ahonen M, Baker AH, Kahari VM
Source: CANCER RESEARCH    Volume: 58    Issue: 11    Pages: 2310-2315    Published: JUN 1 1998  
Times Cited: 169     References: 29     
Abstract: We have used adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinase (TIMP)-1, -2, and -3 to examine their effect on the invasion capacity of metastatic melanoma cell lines SK-Mel-5 and A2058. Infection of melanoma cells with recombinant replication-deficient adenoviruses coding for TIMP-1, TIMP-2, and TIMP-3 resulted in marked secretion of TIMP-1 and TIMP-2 to culture medium and accumulation of TIMP-3 to matrix. Overexpression of TIMP-3 inhibited invasion of SK-Mel-5 and A2058 cells through reconstituted basement membrane (Matrigel) even more potently than TIMP-1 and TIMP-2. In addition, overproduction of TIMP-3 reduced attachment of melanoma cells to type I and IV collagen and fibronectin and resulted in apoptosis in both SK-Mel-5 and A2058 cells. These results propose a novel role for TIMP-3 in regulation of invasion and survival of malignant cells and suggest potential use for TIMP-3 in adenovirus-mediated gene therapy of malignant melanoma.
Document Type: Article
Language: English
Reprint Address: Kahari, VM (reprint author), Univ Turku, Medicity Res Lab, Tykistokatu 6, FIN-20520 Turku, Finland
Addresses:
1. Univ Turku, Medicity Res Lab, FIN-20520 Turku, Finland
2. Univ Turku, Dept Biochem Med, FIN-20520 Turku, Finland
3. Univ Turku, Cent Hosp, Dept Dermatol, FIN-20520 Turku, Finland
4. Bristol Royal Infirm, Bristol Heart Inst, Bristol BS2 8HW, Avon England
Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA
Subject Category: Oncology
IDS Number: ZR703
ISSN: 0008-5472
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