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Novel metastasis model of human lung cancer in SCID mice depleted of NK cells
Author(s) -
Yano Seiji,
Nishioka Yasuhiko,
Izumi Keisuke,
Tsuruo Takashi,
Tanaka Toshiyuki,
Miyasaka Masayuki,
Sone Saburo
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960717)67:2<211::aid-ijc11>3.0.co;2-e
Subject(s) - metastasis , lymph , lymph node , pathology , severe combined immunodeficiency , cancer research , in vivo , cell culture , biology , cancer , cancer cell , medicine , genetics , microbiology and biotechnology
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 × 10 6 ) nor squamous‐cell carcinoma RERF‐LC‐AI cells (1 × 10 6 ), injected through a tail vein, formed metastases in untreated SCID mice. Pre‐treatment of SCID mice with anti‐asialo GM 1 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 GM 1 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 GM 1 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. © 1996 Wiley‐Liss, Inc.