Hepatic clearance and metabolism in the rat of a human breast cancer associated glycoprotein (GCDFP-15).
Gross Cystic Disease Fluid Protein (GCDFP-15) is a 60,000 dalton glycoprotein isolated from human breast cyst fluid, composed of four 15,000 dalton monomers. Carbohydrate analysis indicates that each monomer has a single carbohydrate chain of the complex type. GCDFP-15 intravenously injected into rats showed a rapid circulatory clearance, the rate of clearance being faster in female animals [t1/2 = 12.8 (+/- 2.0) min. females, and 16.7 (+/- 2.6) min. males]. The major organs of clearance were the liver (70%) and kidneys (15%). Immunoperoxidase staining showed localization in Kupffer cells and the proximal convoluted tubules of the kidney. Removal of sialic acid from GCDFP-15 resulted in a more rapid clearance (t1/2 = 2.2 min) by the liver (85%). This clearance was inhibited by coinjection of asialo alpha 1 acid glycoprotein. About 3% of GCDFP-15 was excreted in bile with a transit time through the liver of 38 min. Examination of the uptake of GCDFP-15 by isolated rat Kupffer cells showed that yeast mannan, fucosylated BSA, and carcinoembryonic antigen (CEA) failed to inhibit uptake, though the binding of GCDFP-15 was clearly saturable. This suggests that a novel receptor system on the rat Kupffer cell may be responsible for GCDFP-15 clearance.
Toth
C A
CA
Department of Surgery, New England Deaconess Hospital, Boston, MA 02115.
Haagensen
D E
DE
Davis
S
S
Zamcheck
N
N
Thomas
P
P
D000818:Animals; D001053:Apolipoproteins; D053399:Apolipoproteins D; D001646:Bile / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins; D005260:Female; D006023:Glycoproteins; D006801:Humans; D007728:Kupffer Cells / Q000032:analysis / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D014018:Tissue Distribution
C024328:APOD protein, human; D001053:Apolipoproteins; D053399:Apolipoproteins D; D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; C488892:PIP protein, human