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

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Abstract
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 × 106) nor squamous‐cell carcinoma RERF‐LC‐AI cells (1 × 106), 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 β chain Ab (TM‐β1) 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‐β1 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‐β1 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.

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