Activation of cultured XXXX hepatic stellate cells by tumoral hepatocytes.

@entity35 @entity96 @entity5 @entity1918 @entity11017 @entity10944 @entity1810 @entity1575 @entity157 @entity13963
@entity157 ( @entity157 ) is the main type of primary @entity96 , and it develops from hepatocytes. The stroma of @entity157 is infiltrated by myofibroblasts. In other settings, such as @entity1575 , myofibroblasts are derived mainly from the activation of hepatic stellate cells (HSC). In this study, we investigated whether tumoral hepatocytes were able to activate HSC. HSC were isolated from normal @entity35 and were plated in dishes coated with Matrigel, to prevent their spontaneous activation. HSC were exposed to conditioned medium (CM) from the @entity35 @entity157 lines Fao and H5. Tumor cell CM elicited major morphologic changes, such as spreading and generation of cytoplasmic processes. Fao and H5 CM increased HSC proliferation to 1.60 and 1.76 times control values, respectively. The expression of @entity1918 was low or undetectable in control cells and was markedly increased by both @entity5 cell CM but not by normal @entity35 hepatocyte CM. @entity10944 expression was also enhanced. @entity11017 secretion was significantly increased 1.20-fold by Fao CM and 1.55-fold by H5 CM. Expression of @entity13963 mRNA was increased 5.8-fold by H5 CM but was decreased to 13% of control levels by Fao CM. HSC activation by @entity5 cell CM was not prevented by urokinase or matrix metalloproteinase inhibitors, suggesting that Matrigel degradation was not central to the activation process. Finally, a blocking antibody to @entity1810 did not impede Fao CM-induced activation but significantly blocked the increase in @entity11017 expression induced by H5 CM. Our results show that tumoral @entity35 hepatocyte CM is able to induce the activation of @entity35 HSC in culture. The lack of induction of @entity13963 mRNA by Fao CM indicates that, in some cases, @entity5 -induced activation differs from classic fibrosis-type activation. Our data thus suggest that HSC recruitment and activation in @entity157 could be under the control of @entity5 cells.
