PMID- 11595727
OWN - NLM
STAT- MEDLINE
DCOM- 20011205
LR  - 20220224
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 7
IP  - 10
DP  - 2001 Oct
TI  - Matrilysin mediates extracellular cleavage of E-cadherin from prostate cancer 
      cells: a key mechanism in hepatocyte growth factor/scatter factor-induced 
      cell-cell dissociation and in vitro invasion.
PG  - 3289-97
AB  - PURPOSE: The current study examined the effects of hepatocyte growth 
      factor/scatter factor (HGF/SF) on cell-cell dissociation, invasion, and its 
      association with the mediated release of matrix metalloproteinase-7 (Matrilysin) 
      on the extracellular cleavage of E-cadherin in prostate cancer cells. 
      EXPERIMENTAL DESIGN: The effects of HGF/SF on cell-cell dissociation, in vitro 
      invasion, and on the expression of E-cadherin at both protein and mRNA levels 
      were assessed in cells whose expression of Matrilysin was altered by treatment 
      with antisense oligonucleotide. RESULTS: Incubation with HGF/SF mediated the 
      release of active Matrilysin (M(r) 19,000), resulting in extracellular cleavage 
      of E-cadherin from prostate cancer cells. This resultant soluble M(r) 80,000 
      fragment of E-cadherin was subsequently recognized upon immunoprobing with an 
      anti-E-cadherin antibody. Both recombinant human Matrilysin (rh-Matrilysin) 
      and/or HGF/SF increased the level of soluble E-cadherin and decreased the level 
      of full-length (M(r) 120,000) E-cadherin as detected by Western blotting. The 
      effects of rh-Matrilysin and HGF/SF were inhibited by an antisense 
      oligonucleotide specifically directed toward human Matrilysin. In addition, 
      stimulation with either rh-Matrilysin or HGF/SF resulted in disruption to the 
      E-cadherin/beta-catenin complex, as shown by a significant increase (P < 0.05) in 
      both cell scattering and invasion index. CONCLUSIONS: Treatment with HGF/SF 
      induced Matrilysin-mediated cleavage to the extracellular domain of E-cadherin, 
      resulting in its dissociation from the cadherin/catenin complex. This provides a 
      new mechanism in HGF/SF-induced cell scattering, resulting in a switch to a more 
      invasive phenotype in LNCapFGC cells, as demonstrated by in vitro invasion.
FAU - Davies, G
AU  - Davies G
AD  - Metastasis Research Group, University Department of Surgery, University of Wales 
      College of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK. daviesg11@cf.ac.uk
FAU - Jiang, W G
AU  - Jiang WG
FAU - Mason, M D
AU  - Mason MD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA, Antisense)
RN  - 0 (Mitogens)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 3.4.24.23 (Matrix Metalloproteinase 7)
SB  - IM
MH  - Cadherins/drug effects/*metabolism
MH  - Cell Adhesion/drug effects
MH  - Cell Movement/drug effects
MH  - Culture Media, Conditioned/chemistry
MH  - Cytoskeletal Proteins/drug effects/metabolism
MH  - DNA, Antisense/pharmacology
MH  - Extracellular Space/drug effects/metabolism
MH  - Hepatocyte Growth Factor/pharmacology
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 7/genetics/*metabolism/pharmacology
MH  - Mitogens/pharmacology
MH  - Neoplasm Invasiveness
MH  - Polyethylene Glycols
MH  - Prostatic Neoplasms/*metabolism/pathology
MH  - Recombinant Proteins/pharmacology
MH  - Solubility
MH  - Subcellular Fractions
MH  - Time Factors
MH  - *Trans-Activators
MH  - Tumor Cells, Cultured
MH  - beta Catenin
EDAT- 2001/10/12 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/12 10:00
PHST- 2001/10/12 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/12 10:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 2001 Oct;7(10):3289-97.