Virchows Archiv A

, Volume 412, Issue 6, pp 595–606

Comparative morphology and tumourigenicity of human hepatocellular carcinoma cell lines in athymic rats and mice

  • Daniel Shouval
  • Lucia Schuger
  • Itzhak S. Levij
  • Lola M. Reid
  • Zvi Neeman
  • David A. Shafritz
Article

Summary

Four human hepatoma cell lines PLC/PRF/5, Hep G2, Sk-Hep 1 and Mahlavu were inoculated subcutaneously into athymic Balb/c nude mice and N/NIH outbred nude rats, producing well encapsulated tumours. The 4 hepatoma tumour types in the athymic rodents differ morphologically. PLC/PRF/5 and Hep G2 cells are well differentiated polygonal cells which resemble normal hepatocytes. Tumour arrangement is characterized by solid masses and trabeculae while stromal support is minimal. In contrast, Mahlavu and Sk-Hep 1 tumours have a sarcomatous appearance and consist of spindle shaped cells arranged in solid masses with a rich stromal support. Tumourigenicity of hepatoma cells in the athymic rodents was dependent on injected cell type, inoculation density, relative immunocompetence of the host and the species of animals used. In nude mice, Sk-Hep 1 cells were the most tumourigenic, while Hep G2 cells were tumourigenic only at very high inoculation densities. In nude rats, which were more resistant to tumour formation, PLC/PRF/5 cells were the most tumourigenic. Pre-treatment of athymic mice and rats with total body irradiation resulted in enhanced tumourigenicity for all hepatoma cell lines tested. This was manifested as increased “take” rates, a decreased latency from tumour cell injection to tumour detection, increased tumour weight, and for PLC/PRF/5 cells an increased invasiveness to adjacent body cavities. Furthermore, following irradiation, the minimal number of injected cells required to produce subcutaneous tumours was markedly reduced in both animal species, regardless of tumour cell type. The protocols described enable the reproduceable growth of human hepatoma tumours in athymic rodents.

Key words

Hepatoma Athymic mice Athymic rats 

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Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Daniel Shouval
    • 1
  • Lucia Schuger
    • 2
  • Itzhak S. Levij
    • 2
  • Lola M. Reid
    • 3
  • Zvi Neeman
    • 2
  • David A. Shafritz
    • 3
  1. 1.Liver Unit, Department of Medicine AHadassah University HospitalJerusalemIsrael
  2. 2.Department of PathologyHadassah University HospitalJerusalemIsrael
  3. 3.The Marion Bessin Liver Research Center and Departments of Medicine, Cell Biology and Molecular PharmacologyAlbert Einstein College of MedicineBronxUSA

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