Tamura S, Ouchi K F, Mori K, Endo M, Matsumoto T, Eda H, Tanaka Y, Ishitsuka H, Tokita H, Yamaguchi K
Department of Oncology, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247, Japan.
Clin Cancer Res. 1995 Nov;1(11):1353-8.
A human tumor xenograft model for cancer cachexia was established by growing a uterine cervical carcinoma, Yumoto, in nude mice. The tumor transplanted into the mice induced severe body weight loss (30% of body weight) when the tumor weight was only 1 g. In addition, other indicators for cachexia, such as adipose tissue and muscle wasting and hypoglycemia, were also observed in the tumor-bearing mice, suggesting that this is a proper model for experimental cachexia induced by a human tumor. We then examined the association of this model with various cytokines, such as tumor necrosis factor alpha, interleukin (IL)-1alpha, IL-1beta, IFN-gamma, IL-6, and leukemia inhibitory factor, and identified human IL-6, which was produced by the tumor cells, as a mediator of cachexia. A neutralizing antibody against hIL-6 administered to the mice after the development of cachexia symptoms significantly improved body weight loss, adipose tissue wasting, hypoglycemia, acute phase reaction, and leukocytosis, although it did not suppress the tumor growth. These results demonstrate that the hIL-6 produced by the tumor cells is an essential mediator of the cachexia induction in this model.
通过将子宫颈癌Yumoto种植于裸鼠体内，建立了一种用于癌症恶病质研究的人肿瘤异种移植模型。当肿瘤重量仅为1克时，移植到小鼠体内的肿瘤就导致了严重的体重减轻（体重的30%）。此外，在荷瘤小鼠中还观察到了恶病质的其他指标，如脂肪组织和肌肉消耗以及低血糖，这表明该模型适合用于研究人类肿瘤诱导的实验性恶病质。然后，我们研究了该模型与多种细胞因子的关联，如肿瘤坏死因子α、白细胞介素（IL）-1α、IL-1β、干扰素-γ、IL-6和白血病抑制因子，并确定肿瘤细胞产生的人IL-6是恶病质的介质。在出现恶病质症状后给小鼠注射抗人IL-6中和抗体，虽未抑制肿瘤生长，但显著改善了体重减轻、脂肪组织消耗、低血糖、急性期反应和白细胞增多。这些结果表明，肿瘤细胞产生的人IL-6是该模型中恶病质诱导的关键介质。
