NDLI: Membrane type 1 matrix metalloproteinase induces epithelial-to-mesenchymal transition in prostate cancer.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Richman, Omer Chiarelli, Christian Cao, Jian Kozarekar, Pallavi Zucker, Stanley Zarrabi, Kevin
Description	Author Affiliation: Cao J ( Department of Medicine, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA. jian.cao@sunysb.edu)
Abstract	By mining DNA microarray data bases at GenBank, we identified up-regulation of membrane type 1 matrix metalloproteinase (MT1-MMP) in human primary and metastatic prostate cancer specimens as compared with nonmalignant prostate tissues. To explore the role of up-regulated MT1-MMP in early stage cancer progression, we have employed a three-dimensional cell culture model. Minimally invasive human prostate cancer cells (LNCaP) were transfected with MT1-green fluorescent protein (GFP) chimeric cDNA as compared with GFP cDNA, and morphologic and phenotypic changes were characterized. GFP-expressing LNCaP cells formed multicellular spheroids with cuboidal-like epithelial morphology, whereas MT1-GFP-expressing cells displayed a fibroblast-like morphology and a scattered growth pattern in type I collagen gels. Cell morphologic changes were accompanied by decreased epithelial markers and enhanced mesenchymal markers, consistent with epithelial-to-mesenchymal transition. MT1-MMP-induced morphologic change and cell scattering were abrogated by target inhibition of either the catalytic domain or the hemopexin domain. We further demonstrated that MT1-MMP-induced phenotypic changes were dependent upon up-regulation of Wnt5a, which has been implicated in epithelial-to-mesenchymal transition. We conclude that MT1-MMP plays an important role in early cancer dissemination by converting epithelial cells to migratory mesenchymal-like cells.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	10
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-03-07
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Epithelial Cells Enzymology Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Matrix Metalloproteinase 1 Biosynthesis Models, Biological Prostatic Neoplasms Cell Line, Tumor Cell Movement Genetics Pathology Neoplasm Invasiveness Protein Structure, Tertiary Proto-Oncogene Proteins Spheroids, Cellular Wnt Proteins Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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