Novel metastasis model of human lung cancer in SCID mice depleted of NK cells.
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.
Yano
S
S
Third Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
Nishioka
Y
Y
Izumi
K
K
Tsuruo
T
T
Tanaka
T
T
Miyasaka
M
M
Sone
S
S
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D004195:Disease Models, Animal; D005677:G(M1) Ganglioside / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000276:immunology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D007106:Immune Sera; D015375:Receptors, Interleukin-2; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside