TY - JOUR
T1 - Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration
AU - Mazzocca, Antonio
AU - Carloni, Vinicio
AU - Sciammetta, Silvia Cappadona
AU - Cordella, Claudia
AU - Pantaleo, Pietro
AU - Caldini, Anna
AU - Gentilini, Paolo
AU - Pinzani, Massimo
PY - 2002/9
Y1 - 2002/9
N2 - Background/Aims: Migration of activated hepatic stellate cells (HSC) is a key event in the progression of liver fibrosis. Little is known about transmembrane proteins involved in HSC motility. Tetraspanins (TM4SF) have been implicated in cell development, differentiation, motility and tumor cell invasion. We evaluated the expression and function of four TM4SF, namely CD9, CD81, CD63 and CD151, and their involvement in HSC migration, adhesion, and proliferation. Methods/Results: All TM4SF investigated were highly expressed at the human HSC surface with different patterns of intracellular distribution. Monoclonal antibodies directed against the four TM4SF inhibited HSC migration induced by extracellular matrix proteins in both wound healing and haptotaxis assays. This inhibition was independent of the ECM substrates employed (collagen type I or IV, laminin), and was comparable to that obtained by incubating the cells with an anti-β1 blocking mAb. Importantly, cell adhesion was unaffected by the incubation with the same antibodies. Coimmunoprecipitation studies revealed different patterns of association between the four TM4SF studied and β1 integrin. Finally, anti-TM4SF antibodies did not affect HSC growth. Conclusions: These findings provide the first characterization of tetraspanins expression and of their role in HSC migration, a key event in liver tissue wound healing and fibrogenesis.
AB - Background/Aims: Migration of activated hepatic stellate cells (HSC) is a key event in the progression of liver fibrosis. Little is known about transmembrane proteins involved in HSC motility. Tetraspanins (TM4SF) have been implicated in cell development, differentiation, motility and tumor cell invasion. We evaluated the expression and function of four TM4SF, namely CD9, CD81, CD63 and CD151, and their involvement in HSC migration, adhesion, and proliferation. Methods/Results: All TM4SF investigated were highly expressed at the human HSC surface with different patterns of intracellular distribution. Monoclonal antibodies directed against the four TM4SF inhibited HSC migration induced by extracellular matrix proteins in both wound healing and haptotaxis assays. This inhibition was independent of the ECM substrates employed (collagen type I or IV, laminin), and was comparable to that obtained by incubating the cells with an anti-β1 blocking mAb. Importantly, cell adhesion was unaffected by the incubation with the same antibodies. Coimmunoprecipitation studies revealed different patterns of association between the four TM4SF studied and β1 integrin. Finally, anti-TM4SF antibodies did not affect HSC growth. Conclusions: These findings provide the first characterization of tetraspanins expression and of their role in HSC migration, a key event in liver tissue wound healing and fibrogenesis.
KW - Adhesion molecules
KW - Cell migration
KW - Liver fibrosis
KW - Stellate cells
KW - Tetraspanins
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U2 - 10.1016/S0168-8278(02)00175-7
DO - 10.1016/S0168-8278(02)00175-7
M3 - Article
C2 - 12175627
AN - SCOPUS:0036708281
VL - 37
SP - 322
EP - 330
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 3
ER -