Reduced growth of human sarcoma xenografts in hosts homozygous for the lit mutation
Reduced growth of human sarcoma xenografts in hosts homozygous for the lit mutation
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DOI：
10.1002/jso.10136
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发表时间：
2002-10-01
影响因子：
2.5
通讯作者：
Bell, R
中科院分区：
文献类型：
--
作者：
Deitel, K;Dantzer, D;Bell, R
背景和目的：先前的研究表明胰岛素样生长因子-I（IGF-I）可以刺激肉瘤生长。为了扩展这条线的研究，我们进行了在免疫抑制控制和IGF-I-deficient mice.Methods：人肉瘤标本（骨肉瘤和7个软组织肉瘤）在手术室和植入免疫抑制小鼠体内生长的研究。将第二代肉瘤移植到对照（GH充满litl+小鼠）和实验（GH/IGF-I缺乏lit/lit）动物。当一组肿瘤达到1，000 mm（3）时，比较两组的平均肿瘤大小。IGF-I受体的表达通过RT-PCR和IGF-I受体结合位点进行了测定，放射性标记的IGF-I。结果：8个肉瘤中有5个表现出生长减少GH/IGF-I缺乏的lit/lit动物。在显示生长抑制的五个肉瘤中的四个中，IGF-R相对于胎盘或阳性对照细胞系（MCF-7，已知其在体外和体内对IGF-I有反应）升高。在三个的五个肉瘤，表现出生长抑制，IGF-R升高两倍后，植入实验IGF-I-deficientanimals.Conclusions：生长激素-胰岛素样生长因子轴可能是一个重要的刺激肿瘤生长的肉瘤。这些实验表明，IGF抑制可以抑制体内肉瘤生长。(C)2002 Wiley-Liss，Inc.
Background and Objectives: Prior studies have shown that sarcoma growth can be stimulated by insulin-like growth factor-I (IGF-I). To extend this line of research, we carried out in vivo growth studies of primary human sarcoma in immunosuppressed control and IGF-I-deficient mice.Methods: Human sarcoma specimens (one osteosarcoma and seven soft tissue sarcomas) were harvested in the operating room and implanted in immunosuppressed mice. Second-generation sarcomas were transplanted to control (GH replete litl+ mice) and to experimental (GH/IGF-I-deficient lit/lit) animals. When tumors reached 1,000 mm(3) in one group, average tumor size was compared in the two groups. IGF-I receptor expression was measured by RT-PCR and IGF-I receptor binding sites were assayed by radiolabeled IGF-I.Results: Five of eight sarcomas demonstrated reduced growth in the GH/IGF-I-deficient lit/lit animals. In four of the five sarcomas that demonstrated growth inhibition, IGF-R was elevated relative to placenta or a positive control cell line (MCF-7, which is known to be responsive to IGF-I in vitro and in vivo). In three of the five sarcomas that demonstrated growth suppression, IGF-R was elevated twofold after implantation in the experimental IGF-I-deficient animals.Conclusions: The GH-IGF axis may be an important stimulator of tumor growth in sarcomas. These experiments suggest that IGF suppression may inhibit sarcoma growth in vivo. (C) 2002 Wiley-Liss, Inc.