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Studies on the Mechanism(s) Involved in the Cellular Uptake of Hematoporphyrin and Its Derivatives by Cancer Cells

Research Project

Project/Area Number 61570357
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionKansai Medical University

Principal Investigator

SAMESHIMA Yoshiko  Kansai Med. Univ. Professor and Chairman, 医学部, 教授 (90077602)

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)
Project Period (FY) 1986 – 1988
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1987: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1986: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsCancer Cells / Hematoporphyrin / Hemopexin / Albumin / Hemopexin Receptor / ヘマトボルフィリン / 癌細胞 / ヘモペキシンレセプター / ヘモペキシンリセプター / ラット肝癌細胞 / ヘム
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 … More 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

Report

(4 results)
  • 1989 Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • 1986 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Yuji Naitoh,Yoshiko Sameshima,et al.: "Uptakes of Hematoporphyrin IX and Heme by Rat Hepatoma Cells via Hemopexin Receptor" Cell Structure and Function. 11. 486 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yuji Natioh,Yoshiko Sameshiam,et al.: "Mechanisms Involved in the Cellular Uptake of Hematoporphyrin by Rat Hepatoma Cells" J.Biochem.103. 973-978 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 沢村隆也,鮫島美子,他: "血清アシアロ糖蛋白量よりみた肝硬変重症度判定" 肝臓. 27. 1002 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 内藤雄二,鮫島美子,他: "ラット培養肝癌細胞によるヘマトポルフィリンの取り込み機序について" 肝臓. 28. 844 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 熊田博行,鮫島美子,他: "肝障害時における血漿糖蛋白生合成について" 肝臓. 29. 88 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 中橋佳嗣,鮫島美子,他: "急性肝障害時における肝アシアロ糖蛋白受容体とインスリン受容体の動態" 肝臓. 29. 89 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yuji Naitoh, Yoshiko Sameshima, et al.: "Uptakes of Hematoporphyrin IX and Heme by Rat Hepatoma Cells via Hemopexin Receptor" Cell Structure and Function. 11. 486 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yuji Naitoh, Yoshiko Sameshima, et al.: "Mechanisms Involved in the Cellular Uptake of Hematoporphyrin by Rat Hepatoma Cells" J. Biochem.103. 973-978 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Takaya Sawamura, Yoshiko Sameshima, et al.: "Clinical Application of the Measurement of Serum Asialoglycoproteins to Estimate Liver Function in Patients with Liver Cirrhosis" Acta Hepatologica Japonica. 27. 1002 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yuji Naitoh, Yoshiko Sameshima, et al.: "Mechanism Involved in the Cellular Uptake of Hematoporphyrin by Cultured Rat Hepatoma Cells" Acta Hepatologica Japonica. 29. 844 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hiroyuki Kumada, Yoshiko Sameshima, et al.: "Biosynthesis of the Plasma Glycoproteins During Hepatic Damage" Acta Hepatologica Japonica. 29. 88 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yuji Naitoh.: Cell Structure and Function. 11. 486 (1986)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yuji Naitoh.;Yoshiko Sameshima.;et al.: J.Biocehm.103. 973-978 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 熊田博行、鮫島美子、 他: 肝臓. 29. 88 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 中橋佳嗣、鮫島美子、 他: 肝臓. 29. 89 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yuji Naitoh: Cell Structure and Function. 11. 486 (1986)

    • Related Report
      1987 Annual Research Report
  • [Publications] Yuji Naitoh, Y/shiko Sameshima,et al: J. Biochem.(1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Yuji Naitoh: Cell Structure and Function. 11. 486 (1986)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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