1989 Fiscal Year Final Research Report Summary
Studies on the Mechanism(s) Involved in the Cellular Uptake of Hematoporphyrin and Its Derivatives by Cancer Cells
| Project/Area Number |
61570357
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
SAMESHIMA Yoshiko Kansai Med. Univ. Professor and Chairman, 医学部, 教授 (90077602)
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| Co-Investigator(Kenkyū-buntansha) |
NAITOH Yuji Kansai Med. Univ. Research and Clinical Associate, 医学部, 助手 (30198014)
AOI Kazuo Kansai Med. Univ. Research and Clinical Associate, 医学部, 助手 (70148500)
SAWAMURA Takaya Kansai Med. Univ. Assistant Professor and Lecturer, 医学部, 講師 (10105786)
SHIOZAKI Yasuko Kansai Med. Univ. Associate Professor, 医学部, 助教授 (70077634)
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| Project Period (FY) |
1986 – 1988
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| Keywords | Cancer Cells / Hematoporphyrin / Hemopexin / Albumin / Hemopexin Receptor |
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| Research Abstract |
1. Two serum proteins, hemopexin and albumin, bind to exogdnously administrated hematoporphyrin and serve as carrier in the circulation.
2. Binding study showed the evidence that various tissues or cells as well as hepatocytes process the receptor for hemopexin. Hemopexin and its receptor process are distinct from heioglobin-haptogloblin, iron-transferrin and asialoglycoprotein-receptor systems.
3. Uptake of hematoporphyrin by rat hepatoma cells occurs by two processes between hematoporphyrin-hemopexin and hematoporphyrin-albumin complex. (1) Binding of the hematoporphyrin-hemopexin complex to rat hepatoma cells was specific, with a relative high affinity, Kd: 5.7x10^<-7>M. This affinity was similar to the binding of the heme-hemopexin complex to the cells, and the density of the binding sites for hematoporphyrin-hemopexin complex on the cell surface was similar to that in the case of the heme-hemopexin complex.
Recycling of hemopexin into the medium was also observed when hemo was replac
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ed with hematoporphyrin, as a ligand for hemopexin. These results confirmed that the process of the uptake of hematoporphyrin by rat hepatoma cells from the hematoporphyrin-hemopexin complex is mediated by the hemopexin receptor. Judging from the data of cellular uptake of hematoporphyrin from hematoporphyrin-hemopexin and hematoporphyrin-albumin complex by various cultured cells, cancer cells can oreferentiallytake up hematoporphyrin from hemopexin complex. Quantitative analysis of the hemopexin receptor indicated that increase of the numbers of receptor can result in a relative increase of hematoporphyrin uptake by cancer cells. (2) Albumin-dependent hematoporphyrin uptake by cells seemed to be multiple and complicated since the kinetics of the apparent binding to the cells did not indicate involvement of a single receptor. Mechanism(s) involved in the cellular uptake of hematoporphyrin has been unclear.
4. A hemopexin receptor was purified to the homogeneity from human placenta. This receptor binds heme-hemopexin complex and has a molecular weight of 80 kDa. Immunoinhibition experiments using antibody against the placental receptor revealed inhibition of binding of hemopexin to human leukemia cells, thereby strongly supporting that this protein isolated from placent was hemopexin receptor. Less
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Research Products
(11 results)
