ROLE OF INTERCELLULAR COMMUNICATIONS IN H EPATOCYTE DIFFERENTIATION AND ALTERATIONS DURING CARCINOGENESIS

The liver epoch like other tissue epochs, occurs after that different events have induced heterogeneity in embryonic cells which result in d istinct evolutionnary processes. These events and those of organogenes is like << induction >>, are deeply dependent on cell-cell communicati ons. Cell-cell interactions involve either soluble factors (hormones, growth factors), extracellular matrix or plasma membrane proteins resp onsible for cell-cell recognition and/or adhesion. All these plasma me mbrane signals are transduced to the nucleus and modulate the expressi on of groups of genes. To be functionnally stable along the adult stag e the liver has to maintain an ordered activity of cell renewal. This balance between proliferation and differentiation is at least in part, controlled by cell-cell communications. Therefore, it is not surprisi ng that intercellular communications are altered during hepatocarcinog enesis. They involve changes in the distribution of junctions, in the amounts of extracellular matrix components and/or growth factors which all result in modifying the differentiation/proliferation balance. Ce ll culture models have been used for these different studies ; new in vitro systems should be set up in the near future by taking advantage of the targeted hepatocarcinogenesis in transgenic mouse.