PMID- 19642141
OWN - NLM
STAT- MEDLINE
DCOM- 20100122
LR  - 20160303
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 126
IP  - 5
DP  - 2010 Mar 1
TI  - Monocyte chemoattractant protein-1 (MCP-1)/CCL2 secreted by hepatic 
      myofibroblasts promotes migration and invasion of human hepatoma cells.
PG  - 1095-108
LID - 10.1002/ijc.24800 [doi]
AB  - The aim of our study was to investigate whether myofibroblasts and the chemokine 
      monocyte chemoattractant protein-1 (MCP-1)/CCL2 may play a role in hepatocellular 
      carcinoma progression. We observed that hepatic myofibroblast LI90 cells express 
      MCP-1/CCL2 mRNA and secrete this chemokine. Moreover, myofibroblast LI90 
      cell-conditioned medium (LI90-CM) induces human hepatoma Huh7 cell migration and 
      invasion. These effects are strongly reduced when a MCP-1/CCL2-depleted LI90-CM 
      was used. We showed that MCP-1/CCL2 induces Huh7 cell migration and invasion 
      through its G-protein-coupled receptor CCR2 and, to a lesser extent, through CCR1 
      only at high MCP-1/CCL2 concentrations. MCP-1/CCL2's chemotactic activities rely 
      on tyrosine phosphorylation of focal adhesion components and depend on matrix 
      metalloproteinase (MMP)-2 and MMP-9. Furthermore, we observed that Huh7 cell 
      migration and invasion induced by the chemokine are strongly inhibited by 
      heparin, by beta-D-xyloside treatment of cells and by anti-syndecan-1 and -4 
      antibodies. Finally, we developed a 3-dimensional coculture model of 
      myofibroblast LI90 and Huh7 cells and demonstrated that MCP-1/CCL2 and its 
      membrane partners, CCR1 and CCR2, may be involved in the formation of mixed 
      hepatoma-myofibroblast spheroids. In conclusion, our data show that human liver 
      myofibroblasts act on hepatoma cells in a paracrine manner to increase their 
      invasiveness and suggest that myofibroblast-derived MCP-1/CCL2 could be involved 
      in the pathogenesis of hepatocellular carcinoma.
FAU - Dagouassat, Maylis
AU  - Dagouassat M
AD  - INSERM U698, Bioingenierie cardiovasculaire, Universite Paris 13, Bobigny, 
      France.
FAU - Suffee, Nadine
AU  - Suffee N
FAU - Hlawaty, Hanna
AU  - Hlawaty H
FAU - Haddad, Oualid
AU  - Haddad O
FAU - Charni, Faten
AU  - Charni F
FAU - Laguillier, Christelle
AU  - Laguillier C
FAU - Vassy, Roger
AU  - Vassy R
FAU - Martin, Loic
AU  - Martin L
FAU - Schischmanoff, Pierre-Olivier
AU  - Schischmanoff PO
FAU - Gattegno, Liliane
AU  - Gattegno L
FAU - Oudar, Olivier
AU  - Oudar O
FAU - Sutton, Angela
AU  - Sutton A
FAU - Charnaux, Nathalie
AU  - Charnaux N
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
SB  - IM
MH  - Carcinoma, Hepatocellular/*metabolism/pathology
MH  - Cell Movement/*physiology
MH  - Chemokine CCL2/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibroblasts/*metabolism
MH  - Flow Cytometry
MH  - Humans
MH  - Liver/cytology/metabolism
MH  - Liver Neoplasms/*metabolism/pathology
MH  - Neoplasm Invasiveness/physiopathology
MH  - RNA Interference
MH  - Surface Plasmon Resonance
EDAT- 2009/07/31 09:00
MHDA- 2010/01/23 06:00
CRDT- 2009/07/31 09:00
PHST- 2009/07/31 09:00 [entrez]
PHST- 2009/07/31 09:00 [pubmed]
PHST- 2010/01/23 06:00 [medline]
AID - 10.1002/ijc.24800 [doi]
PST - ppublish
SO  - Int J Cancer. 2010 Mar 1;126(5):1095-108. doi: 10.1002/ijc.24800.