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Hepatic clearance and metabolism in the rat of a human breast cancer associated glycoprotein (GCDFP-15)

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Summary

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 alpha1 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.

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Authors and Affiliations

  1. Laboratory of Cancer Biology, Department of Surgery, New England Deaconess Hospital, 50 Binney Street, 02115, Boston, MA, USA

    Carol A. Toth, Darrow E. Haagensen Jr., Sarah Davis, Norman Zamcheck & Peter Thomas

  2. Mallory Gastrointestinal Research Laboratory, Boston City Hospital, 02115, Boston, MA, USA

    Carol A. Toth, Darrow E. Haagensen Jr., Sarah Davis, Norman Zamcheck & Peter Thomas

  3. Departments of Surgery and Medicine, Harvard Medical School, 02115, Boston, MA, USA

    Carol A. Toth, Darrow E. Haagensen Jr., Sarah Davis, Norman Zamcheck & Peter Thomas

Authors
  1. Carol A. Toth
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  2. Darrow E. Haagensen Jr.
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  3. Sarah Davis
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  4. Norman Zamcheck
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  5. Peter Thomas
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Toth, C.A., Haagensen, D.E., Davis, S. et al. Hepatic clearance and metabolism in the rat of a human breast cancer associated glycoprotein (GCDFP-15). Breast Cancer Res Tr 12, 235–243 (1988). https://doi.org/10.1007/BF01805944

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