Cellular aspects of alpha-fetoprotein reexpression in tumors

The cellular basis of AFP synthesis in normal development, liver regeneration, hepatocarcinogenesis and in tumors is discussed in the review. The attempt is made to interpret the production of AFP by germ cell and liver tumors as a consequence of their origin from the cell types producing AFP in normal conditions. Thus, AFP in germ cell tumors is explained by the development of the yolk sac visceral endoderm (YSVE) in teratocarcinomas, since YSVE is the first site of AFP synthesis in the embryo. The next site of AFP production is embryonal hepatoblast and just hepatoblastomas are the maximal producers of AFP among liver cancers. The reason for AFP resumption in hepatocellular carcinomas (HCC) is not yet clear. This problem is discussed in the light of possible role of oval cells in the HCC origin and the concept of the two states of the mature hepatocyte, associated and non-associated with AFP production. The crucial role of extracellular matrix in the control of AFP-producing state of hepatocyte is emphasized.