Retroviral delivery of TIMP-2 inhibits H-ras-induced migration and invasion in MCF10A human breast epithelial cells

The matrix metalloproteases (MMPs) play important roles in invasion, metastasis and angiogenesis in various cell types. Tissue inhibitor of metalloprotease (TIMP)-2, an endogenous inhibitor of MMP-2, has been shown to inhibit invasion and metastasis. We have previously shown that MMP-2 is responsibl...

Full description

Saved in:
Bibliographic Details
Published in:Cancer letters 2004-04, Vol.207 (1), p.49-57
Main Authors: Ahn, Seong-Min, Jeong, Seo-Jin, Kim, Yeon-Soo, Sohn, Yeowon, Moon, Aree
Format: Article
Language:English
Subjects:
Angiogenesis
Breast cancer
Cell Line
Cell Line, Transformed
Cell Line, Tumor
Cell Movement
Cells, Cultured
Collagen
Disease Progression
Dose-Response Relationship, Drug
Endothelium, Vascular - cytology
Gene therapy
Gene Transfer Techniques
Genetic Therapy
Humans
Immunoblotting
Invasion
Migration
Models, Genetic
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasms - therapy
Neovascularization, Pathologic
Phenotype
ras Proteins - metabolism
Retroviridae - genetics
Retrovirus
Tetrazolium Salts - pharmacology
Thiazoles - pharmacology
Time Factors
TIMP-2
Tissue Inhibitor of Metalloproteinase-2 - metabolism
Wound Healing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The matrix metalloproteases (MMPs) play important roles in invasion, metastasis and angiogenesis in various cell types. Tissue inhibitor of metalloprotease (TIMP)-2, an endogenous inhibitor of MMP-2, has been shown to inhibit invasion and metastasis. We have previously shown that MMP-2 is responsible for the H-ras-induced invasive and migrative phenotypes in MCF10A human breast epithelial cells. Here, we investigated the effect of TIMP-2 overexpression on migration and invasion in H-ras MCF10A cells. Human TIMP-2 gene was effectively introduced into H-ras MCF10A cells by retrovirus-mediated gene delivery. TIMP-2 overexpression mediated by retrovirus significantly inhibited migration as well as invasion of H-ras MCF10A cells in a dose-dependent manner. We also show the antiangiogenic effect of TIMP-2 gene delivery. Taken together, our study shows that retrovirus-mediated delivery of TIMP-2 efficiently inhibits metastatic progression of ras-transformed human breast epithelial cells, suggesting a potential use of the TIMP-2 gene therapy for the treatment of breast cancer.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2003.11.025