Tinkey P T, Milas M, Pollock R E
Department of Veterinary Medicine and Surgery The University of Texas M. D. Anderson Cancer Center 1515 Holcombe Blvd. Houston TX 77030 USA.
Sarcoma. 1999;3(2):129-33. doi: 10.1080/13577149977767.
Purpose. The ability to establish consistent human tumor xenografts in experimental animals is a crucial part of preclinical investigations.The goal of this study was to develop a method of establishing a human tumor xenograft in the leg of a nude rat for evaluation of new surgical and molecular methods of treatments of human extremity sarcoma.Methods and results. Initial attempts to produce sarcoma nodules by subcutaneous injection of a human leiomyosarcoma tumor cell suspension (SKLMS-1) resulted in tumor nodule formation in only four of 10 sites (40%).The xenograft method was modified to include younger nude rats of a different source and substrain (HSD:rnu/rnu, 5-9 weeks old), treated with 500 cGy whole-body irradiation, and the transplantation of tumor cells or small tumor fragments which had been embedded in Matrigel.These changes improved the tumor take rate per site to 52/52 (100%).Tumor nodules demonstrated rapid and progressive growth and histological features consistent with the original human sarcoma.Discussion. Successful human leiomyosarcoma establishment in these nude rats permits the investigation of sarcoma biology and treatment with surgical procedures for which a mouse model would be inadequate. In this study we identified modifications in technique which enhanced the xenografting of a leiomyosarcoma cell line in nude rats; these techniques may increase tumor take rates for other tumor types as well.
目的。在实验动物中建立稳定的人肿瘤异种移植模型的能力是临床前研究的关键部分。本研究的目的是开发一种在裸鼠腿部建立人肿瘤异种移植模型的方法,以评估治疗人类肢体肉瘤的新手术和分子方法。方法与结果。最初通过皮下注射人平滑肌肉瘤肿瘤细胞悬液(SKLMS-1)来产生肉瘤结节,在10个部位中只有4个部位(40%)形成了肿瘤结节。异种移植方法进行了改进,包括使用不同来源和亚系的更年轻裸鼠(HSD:rnu/rnu,5-9周龄),给予500 cGy全身照射,并移植包埋在基质胶中的肿瘤细胞或小肿瘤碎片。这些改变使每个部位的肿瘤接种成功率提高到52/52(100%)。肿瘤结节显示出快速且渐进性生长,组织学特征与原始人肉瘤一致。讨论。在这些裸鼠中成功建立人平滑肌肉瘤模型,使得能够研究肉瘤生物学,并使用小鼠模型不适用的手术方法进行治疗。在本研究中,我们确定了技术上的改进,这些改进增强了平滑肌肉瘤细胞系在裸鼠中的异种移植;这些技术也可能提高其他肿瘤类型的肿瘤接种成功率。