Autonomous cholesterol biosynthesis in murine hepatoma. A receptor defect with normal coated pits.
These studies indicate that autonomous cholesterol biosynthesis by hepatocellular carcinoma may result from absent or defective receptors for chylomicron remnants on the surface of the malignant hepatocytes. In vivo, DAB2 hepatoma or liver were perfused with chylomicron remnants labeled with tritiated palmitic acid. Normal liver had chylomicron remnant uptake/gm tissue that was ten times that of hepatoma. In vitro studies using isolated hepatocytes and cultured DAB2 hepatoma cells showed similar results. Uptake of chylomicron remnants labeled with 3H-palmitic acid by normal hepatocytes during a 4-hour period was ten times that of hepatoma cells. Both in vivo and in vitro differences were statistically highly significant (P less than 0.005). Since many surface receptors are related to the coated pits, the cellular membranes of both neoplastic and normal liver cells were examined by electron microscopy. Coated pits were present in both the hepatoma and normal liver cells and occupied 2.61% and 2.65% of the cell surface, respectively. The defective uptake of chylomicron remnants by DAB2 hepatoma appears to be related to the chylomicron remnant receptor and not to the coated pit-internalization mechanism.
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis*; D003034:Coated Pits, Cell-Membrane / Q000648:ultrastructure; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein
D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C028203:chylomicron receptor; D002784:Cholesterol