Weber Kristy L, Pathak Sen, Multani Asha S, Price Janet E
Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
J Urol. 2002 Aug;168(2):774-9.
We provide the necessary tools to study the biology of bone metastasis using renal cell carcinoma as a model. A relevant renal cell carcinoma cell line developed from a human bone metastasis is described and an experimental model in the nude mouse was established.
The novel cell line RBM1 was developed from bone metastasis from a patient with renal cell carcinoma. In vitro methods used to study the cell line included karyotype analysis, reverse-transcriptase polymerase chain reaction, ribonuclease protection assay and Western blot analysis. An intratibial injection model in the nude mouse resulted in bone lesions similar to those in human patients.
Chromosomal analysis of this cell line revealed characteristic cytogenetic abnormalities common in renal cell carcinoma. RBM1 cells expressed parathyroid hormone parathyroid hormone related peptide, interleukin-6 and macrophage colony-stimulating factor, which are cytokines involved in osteoclast activation and subsequent bone resorption. Western blot analysis revealed the presence of high levels of epidermal growth factor receptor and c-MET. Reproducible osteolytic lesions developed in the nude mouse after injecting 1 x 106 cells into the tibia.
This cell line and animal model may allow further study of the biology and mechanism of renal cell carcinoma bone metastasis.
我们提供必要的工具,以肾细胞癌为模型研究骨转移生物学。描述了一种从人骨转移灶中培养出的相关肾癌细胞系,并建立了裸鼠实验模型。
新型细胞系RBM1是从一名肾细胞癌患者的骨转移灶中培养出来的。用于研究该细胞系的体外方法包括核型分析、逆转录聚合酶链反应、核糖核酸酶保护试验和蛋白质免疫印迹分析。裸鼠胫骨内注射模型产生了与人类患者相似的骨病变。
该细胞系的染色体分析显示出肾细胞癌常见的特征性细胞遗传学异常。RBM1细胞表达甲状旁腺激素、甲状旁腺激素相关肽、白细胞介素-6和巨噬细胞集落刺激因子,这些细胞因子参与破骨细胞活化及随后的骨吸收。蛋白质免疫印迹分析显示存在高水平的表皮生长因子受体和c-MET。将1×10⁶个细胞注射到裸鼠胫骨后,产生了可重复性的溶骨性病变。
该细胞系和动物模型可能有助于进一步研究肾细胞癌骨转移的生物学特性和机制。