Novel metastasis model of human lung cancer in SCID mice depleted of NK cells

Int J Cancer. 1996 Jul 17;67(2):211-7. doi: 10.1002/(SICI)1097-0215(19960717)67:2<211::AID-IJC11>3.0.CO;2-E.


Metastasis is a critical problem in the treatment of human lung cancer. Thus, a suitable animal model of metastasis of human lung cancer is required for in vivo biological and preclinical studies. In this study, we tried to establish a suitable model for this, using SCID mice. Neither human SCLC H69/VP cells (5 x 10(6)) nor squamous-cell carcinoma RERF-LC-AI cells (1 x 10(6)), injected through a tail vein, formed metastases in untreated SCID mice. Pre-treatment of SCID mice with anti-asialo GM1 serum resulted in only a few metastases of H69/VP cells, but pre-treatment with anti-mouse IL-2 receptor beta chain Ab (TM-beta 1) resulted in numerous lymph-node metastases 56 days after tumor inoculation. H69/VP-M cells, an in vivo-selected variant line, formed significant numbers of lymph-node metastases even in SCID mice pre-treated with anti-asialo GM1 serum. SCID mice depleted of NK cells by treatment with TM-beta 1 showed different patterns of metastasis when inoculated intravenously with the 2 different human lung cancer cell lines (H69/VP and RERF-LC-AI cells): H69/VP cells formed metastases mainly in systemic lymph nodes and the liver, whereas RERF-LC-AI cells formed metastases mainly in the liver and kidneys, with only a few in lymph nodes. A histopathological study showed that the metastatic colonies consisted of cancer cells. The numbers of metastatic colonies formed by the 2 cell lines increased with the number of cells inoculated. TM-beta 1 treatment of SCID mice efficiently removed NK cells from peripheral blood for at least 6 weeks, whereas, after treatment of the mice with anti-asialo GM1 serum, NK cells were recovered within 9 days. These findings suggest that NK-cell-depleted SCID mice may be useful as a model in biological and pre-clinical studies on metastasis of human lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Disease Models, Animal*
  • G(M1) Ganglioside / immunology
  • Humans
  • Immune Sera / pharmacology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Liver Neoplasms / secondary
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis / immunology
  • Male
  • Mice
  • Mice, SCID
  • Neoplasm Metastasis / immunology*
  • Receptors, Interleukin-2 / immunology
  • Tumor Cells, Cultured


  • Antibodies
  • Immune Sera
  • Receptors, Interleukin-2
  • G(M1) Ganglioside
  • asialo GM1 ganglioside