Ceruloplasmin contains the majority of the copper in plasma or serum in humans and animals. Ceruloplasmin levels are markedly increased in pregnancy and cancer, with smaller increases occurring in some other disease states. We have demonstrated that this glycoprotein is the main source of copper for most normal and malignant cells. Turnover of ceruloplasmin copper is rapid, especially in rats with implanted tumors, and substantial amounts of copper accumulate in tumors. Since certain forms of copper chelates are known to inhibit tumor growth, the question arises whether ceruloplasmin or the other forms of serum copper play a role in host defense or, conversely, promote cell proliferation. Since the renewal of this grant, we have made two important additional discoveries about copper components in mammalian serum. First, we have found an additional copper transport protein that appears to function, with albumin, in the transport of dietary copper from the intestine to the liver, where it is incorporated into ceruloplasmin (reappearing in the plasma for further distribution). Second, we have established that, contrary to dogma established in the '50s (using flame atomic absorption and low specific activity copper radioisotopes), ceruloplasmin comprises not 90 to 95% but only about 60% of the total copper in plasma, with substantial additional quantities in albumin and the new copper transport protein fraction (about 15% each) and another 10% or so in components of low molecular weight. The present work is focusing on the purification and characterization of the new copper transport protein of rat and human serum, tentatively named """"""""transcuprein,"""""""" and on the mechanisms by which ceruloplasmin copper is taken up by cells. With regard to the latter, we are working on the hypothesis that mammalian cells have surface receptors for ceruloplasmin that allow specific binding of ceruloplasmin and transfer of its copper to the cell, either by internalization or by surface transfer. (J)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA022410-06S1
Application #
3165818
Study Section
Pathology B Study Section (PTHB)
Project Start
1978-09-01
Project End
1985-11-30
Budget Start
1984-04-01
Budget End
1985-11-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
California State University Fullerton
Department
Type
Schools of Arts and Sciences
DUNS #
106670755
City
Fullerton
State
CA
Country
United States
Zip Code
92831
Linder, M C; Roboz, M (1986) Turnover and excretion of copper in rats as measured with 67Cu. Am J Physiol 251:E551-5
Orena, S J; Goode, C A; Linder, M C (1986) Binding and uptake of copper from ceruloplasmin. Biochem Biophys Res Commun 139:822-9
Wirth, P L; Linder, M C (1985) Distribution of copper among components of human serum. J Natl Cancer Inst 75:277-84