在NSG 鼠中人黑素瘤的转移与患者的临床治疗效果有关

Human Melanoma Metastasis in NSG Mice Correlates with Clinical Outcome in Patients Abstract

Studies of human cancer metastasis have been limited by a lack of experimental assays （in which cancer cells from patients metastasize in vivo ）in a way that correlates with clinical outcome. This makes it impossible to study intrinsic differences in the metastatic properties of cancers from different patients. We recently developed an assay in which human melanomas readily engraft in nonobese diabetic/severe combined immunodeficient interleukin-2 receptor-γchain null (NSG) mice. We show that melanomas from 25 patients exhibited reproducible differences in the rate of spontaneous metastasis after transplantation into NSG mice and that these differences correlated with clinical outcome in the patients. Stage IIIB/C melanomas that formed distant metastases within 22 months in patients also formed tumors that metastasized widely in NSG mice, whereas stage IIIB/C melanomas that did not form distant metastases within 22 to 50 months in patients metastasized more slowly in NSG mice.

The study of NSG mice can therefore yield information about the metastasis of human melanomas in vivo, in this case revealing intrinsic differences among stage IIIB/C melanomas in their ability to circulate/survive in the blood and to metastasize.

在NSG 鼠中人黑素瘤的转移与患者的临床治疗效果有关

摘要

由于缺乏对患者癌细胞体内转移（在某种程度上和临床疗效有关）的实验分析，人癌症转移的相关研究受到限制。这使得对来自不同患者的肿瘤的转移性本质区别的研究变得不可能。在近期展开的试验分析中，我们将人黑素瘤植入非肥胖型糖尿病/重症免疫缺陷、白细胞介素-2受体γ链缺失（NSG）小鼠中。我们的研究显示，来自于25位患者的黑素瘤，在移植入NSG小鼠体内后，显示出自发性转移速率的可再现差异，这些差异与患者的临床治疗效果有关。这些转移效率的差异，与NSG小鼠血液中循环黑素瘤细胞的存在密切相关。这表明，人黑色素瘤细胞进入血液的速率是限制转移速率的一个因素。因此，对NSG小鼠的研究（如在本例中，揭示了IIIB/C期黑素瘤在血液中循环或生存以及转移能力的内在差异），可以得到人黑素瘤体内转移的信息。