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  • Title: Direct demonstration of negative regulation of tumor growth and metastasis by host-inducible nitric oxide synthase.
    Author: Wei D, Richardson EL, Zhu K, Wang L, Le X, He Y, Huang S, Xie K.
    Journal: Cancer Res; 2003 Jul 15; 63(14):3855-9. PubMed ID: 12873972.
    Abstract:
    Inducible nitric oxide synthase (NOS) II expression can be induced in the tumor bed, predominantly in host cells that infiltrate and surround a tumor. However, the impact of this physiological NOS II expression in host cells on tumor growth and metastasis remains unclear because of a lack of appropriate experimental approaches. In the present study, three NOS II-null (NOS II(-/-)) tumor cell lines, KX-dw1, KX-dw4, and KX-dw7, were established and verified using Southern, Northern, and Western blot analysis, and nitric oxide production assays. Cells from these lines were then s.c. and i.v. injected into NOS II(+/+) and NOS II(-/-) C57BL/6 mice. NOS II protein expression and enzyme activity were clearly detected in the tumors that formed in NOS II(+/+) mice but not in those that formed in NOS II(-/-) mice. Consistent with the absence of NOS II expression in the tumor stroma, KX-dw1, KX-dw4, and KX-dw7 cells grew much faster and produced many more experimental lung metastases in NOS II(-/-) mice than in NOS II(+/+) mice. Therefore, physiological expression of NOS II in host cells directly inhibits tumor growth and metastasis.
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