Inhibition of B16 melanoma experimental metastasis by interferon-γ through direct inhibition of cell proliferation and activation of antitumour host mechanisms
Inhibition of B16 melanoma experimental metastasis by interferon-γ through direct inhibition of cell proliferation and activation of antitumour host mechanisms
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DOI：
10.1046/j.0019-2805.2001.01342.x
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发表时间：
2002-01-01
期刊：
影响因子：
6.4
通讯作者：
Iwakura, Y
中科院分区：
文献类型：
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作者：
Kakuta, S;Tagawa, Y;Iwakura, Y
干扰素-γ（IFN-γ）除了其抗病毒作用之外还具有多效性活性，包括细胞生长抑制、自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）活化以及血管生成抑制活性，并且这些活性被认为与其抗肿瘤活性有关。然而，尚未完全阐明哪种活性主要参与体内肿瘤抑制。在这项研究中，我们分析了内源性IFN-γ对B16黑色素瘤实验转移的抑制机制。静脉注射肿瘤细胞后，IFN-gamma（-/-）小鼠肺部和肝脏中的肿瘤沉积增加，寿命缩短，这表明IFN-gamma在抗肿瘤机制中发挥重要作用。有趣的是，在IFN-γ受体（R）（-/-）小鼠中肿瘤沉积物没有增加。此外，仅观察到低水平的细胞介导的抗肿瘤免疫和NK细胞的活化，表明IFN-γ的抗转移作用不由宿主细胞介导。然而，携带B16黑色素瘤的IFN-gammaR（-/-）小鼠的生存期比野生型小鼠短。这些观察结果表明，IFN-γ通过直接抑制细胞生长来预防B16黑色素瘤实验性转移，尽管抗肿瘤宿主功能也可能在后期参与。
Interferon-gamma (IFN-gamma) has pleiotropic activities other than its antivirus action, including cell growth inhibition, natural killer (NK) cell and cytotoxic T lymphocyte (CTL) activation, and angiogenesis inhibitory activity, and these activities are supposed to be involved in its antitumour activity. However, it has not been completely elucidated which activity is mainly involved in the tumour suppression in vivo. In this study, we analysed inhibitory mechanisms of endogenous IFN-gamma against B16 melanoma experimental metastasis. After intravenous injection of tumour cells, tumour deposits in the lungs and liver were increased and life span was shorter in IFN-gamma(-/-) mice, indicating important roles for IFN-gamma in antitumour mechanisms. Interestingly, tumour deposits were not increased in IFN-gamma receptor (R)(-/-) mice. Furthermore, only low levels of cell-mediated immunity against the tumour and activation of NK cells were observed, indicating that antimetastatic effects of IFN-gamma is not mediated by host cells. The survival period of B16 melanoma-bearing IFN-gammaR(-/-) mice was, however, shorter than wild-type mice. These observations suggest that IFN-gamma prevents B16 melanoma experimental metastasis by directly inhibiting the cell growth, although antitumour host functions may also be involved in a later phase.