Synthesis of alpha-fetoprotein in hepatocytes is co-ordinately regulated with cell-cell and cell-matrix interactions.

The synthesis of alpha-fetoprotein in primary cultures of adult mouse hepatocytes was studied under different conditions of cultivation. On dried collagen, the majority of cells resumed synthesis of alpha-fetoprotein. Alpha-fetoprotein re-expression was accompanied by the flattening of hepatocytes, loss of gap junctional communication and domain-specific membrane antigens, and by alteration of actin pattern. Cultivation of hepatocytes on polymerized collagen gel did not prevent the re-expression of alpha-fetoprotein and other alterations described above. Hepatocyte cultivation within three-dimensional collagen gel as well as co-cultivation of hepatocytes with liver epithelial cells IAR-20 led to re-establishment of organotypic trabeculae-like structures consisting of polygonal hepatocytes with normal pattern of actin, membrane antigens and cell-cell communication. These structures were almost alpha-fetoprotein-negative. It is suggested that hepatocyte shape is co-ordinately regulated with the switch from an adult "block" of hepatocyte functions to an embryonic one. Three-dimensional extracellular matrix may in turn, influence the maintenance of hepatocyte shape.