PMID- 21413933
OWN - NLM
STAT- MEDLINE
DCOM- 20110722
LR  - 20231213
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 121
IP  - 4
DP  - 2011 Aug
TI  - Hepatic stellate cells stimulate HCC cell migration via laminin-5 production.
PG  - 159-68
LID - 10.1042/CS20110002 [doi]
AB  - Activated HSCs (hepatic stellate cells) are the main source of extracellular 
      matrix proteins present in cirrhotic liver on which HCC (hepatocellular 
      carcinoma) commonly develops. HCC cells behave differently according to 
      differences in the surrounding microenvironment. In the present study, we have 
      investigated a mechanism whereby HSCs modulate the migratory activity of HCC 
      cells. We used primary cultures of human HSCs to investigate their effect on 
      Hep3B, Alexander, HLE and HLF HCC cells. The expression of Ln-5 (laminin-5) was 
      documented at transcript and protein levels both in vitro and in vivo. HCC cells 
      strongly adhere, migrate and spread in the presence of HSC-conditioned medium and 
      of co-culture. HSCs produce and secrete Ln-5 in the CM (conditioned medium). The 
      electrophoretic pattern of secreted Ln-5 is consistent with that of a migratory 
      substrate, showing the presence of the gamma2x fragment. Blocking antibodies against 
      Ln-5 inhibit HCC migration in the presence of HSC-CM. HCC cells migrate very 
      poorly in the presence of Ln-5 immunodepleted HSC-CM. HCC migration in the 
      presence of HSCs is dependent on the MEK [MAPK (mitogen-activated protein 
      kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK pathway, but not 
      the PI3K (phosphoinositide 3-kinase)/Akt pathway. HSC-CM, as well as Ln-5, 
      activates the MEK/ERK but not the PI3K/Akt pathway. In human HCC tissues, Ln-5 is 
      mainly distributed along alpha-SMA (smooth muscle actin)-positive cells, whereas in 
      peritumoural tissues, Ln-5 is absent. HSCs stimulate HCC migration via the 
      production and secretion of Ln-5.
FAU - Santamato, Angela
AU  - Santamato A
AD  - Department of Internal Medicine, Immunology and Infectious Diseases, Section of 
      Internal Medicine, University of Bari Medical School, Bari, Italy.
FAU - Fransvea, Emilia
AU  - Fransvea E
FAU - Dituri, Francesco
AU  - Dituri F
FAU - Caligiuri, Alessandra
AU  - Caligiuri A
FAU - Quaranta, Michele
AU  - Quaranta M
FAU - Niimi, Tomoaki
AU  - Niimi T
FAU - Pinzani, Massimo
AU  - Pinzani M
FAU - Antonaci, Salvatore
AU  - Antonaci S
FAU - Giannelli, Gianluigi
AU  - Giannelli G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Culture Media, Conditioned)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Hepatocellular/metabolism/*pathology
MH  - Cell Adhesion/physiology
MH  - Cell Adhesion Molecules/*biosynthesis/physiology
MH  - Cell Movement/*physiology
MH  - Coculture Techniques
MH  - Culture Media, Conditioned
MH  - Hepatic Stellate Cells/*physiology
MH  - Humans
MH  - Liver Neoplasms/metabolism/*pathology
MH  - Middle Aged
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Tumor Cells, Cultured
MH  - Kalinin
EDAT- 2011/03/19 06:00
MHDA- 2011/07/23 06:00
CRDT- 2011/03/19 06:00
PHST- 2011/03/19 06:00 [entrez]
PHST- 2011/03/19 06:00 [pubmed]
PHST- 2011/07/23 06:00 [medline]
AID - CS20110002 [pii]
AID - 10.1042/CS20110002 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2011 Aug;121(4):159-68. doi: 10.1042/CS20110002.