[alpha-Fetoprotein (biology)].
The paper gives a historical overview of the origin and experimental analysis of alpha-fetoprotein (AFP) regulation and its reexpression in malignant tumors. It shows how a specific hepatoma-specific antigen that was later identified as the major protein component of embryonic serum was found and isolated during searches for murine hepatoma-specific antigens. Later on it was shown that AFP was synthesized by the yolk sac endoderm of the embryo and, later, by the fetal liver and its synthesis drastically diminishes in the adult animal liver. AFP synthesis restores in the moderately differentiated hepatomas and temporarily in the murine regenerating liver. The same regularity, but in other quantitative ratio, occurs in man. Analyzing the causes of AFP reexpression in the regenerating liver has indicated that suppression of AFP synthesis in the mature hepatocytes is reversible and controlled by the position of a hepatocyte in the liver plate: when the hepatocyte is included into the plate, it becomes fully differentiated with AFP suppression. Hepatocytic isolation from the plate leads to its "dedifferentiation" and AFP reexpression. AFP reexpression takes place in the perinecrotic cell layer in the liver poisoned by CCl4. Hepatocytic isolation from the liver and explantation into the cultured tissue results in strong reexpression of AFP while incorporation of the isolated hepatocytes in the three-dimensional extracellular matrix (ECM) leads to AFP suppression together with hepatocytic "maturation". Hepatocytic interaction with defective ECM does not suppress AFP synthesis. Our hypothesis suggests that disturbance of cell-ECM interactions during transformation and tumor progression is the main reason of AFT reappearance in liver tumors.
Abelev
G I
GI
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D000509:alpha-Fetoproteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins