细胞角质蛋白19与肝癌模型生长转移关系的探讨

Study on the relationship between serum cytokeratin19 level in tumor-bearing nude mice and pulmonary metastasis

目的 分析荷瘤裸鼠血清中细胞角质蛋白 19(CK19)的浓度变化与肿瘤转移的关系。方法 将 3次肺转移筛选的人肝细胞癌 (HCC)细胞株 (HCCLM 3 )接种于 3 0只BALB/c nu/nu裸小鼠皮下 ,随机分 6组 ,于接种后 2、3、4、5、6、7周分别处死 1组 ,用放射性核素标记的免疫吸附试验(ELISA)检测裸鼠血清中CK19浓度 ,并称量肿瘤重量、肺组织连续切片检查转移率。结果 接种细胞后各时点的肿瘤重量依次为 (0 .3 1± 0 .13 )、(0 .61± 0 .12 )、(1.43± 0 .3 7)、(2 .3 8± 0 .92 )、(3 .74± 0 .96)、(4 .85± 1.0 2 )g ;肺转移率依次为 0、0、2 0 %、10 0 %、10 0 %、10 0 % ;在第 5、6、7周时每只裸小鼠肺转移灶中位数依次为 81、118、15 0个 ;裸鼠血清中CK19浓度依次为 (4 .79± 1.16)、(5 .0 6± 1.2 1)、(8.5 5± 1.2 5 )、(4 0 .71± 9.87)、(76.2 9± 2 0 .0 0 )、(95 .94± 19.68) μg/L ,在出现转移时CK19浓度明显升高 (P <0 .0 1)。结论 荷瘤裸鼠外周血中CK19浓度与肿瘤进展呈明显正相关性 ,当发生肺转移时明显升高 。

Objective To explore the relationship between serum cytokeratin 19 level in tumor bearing nude mice and the development of pulmonary metastasis.Methods Human hepatocellular carcinoma cells from HCCLM3 were injected subcutaneously into 30 BALB/C nu/nu mice,which were then randomized into 6 groups of 5 mice in each.The mice were killed 2,3,4,5,6,and 7 weeks after injection,respectively,and the serum CK19 level,tumor weight,and pulmonary metastases were determined using radioimmunoassay and conventional histopathological examinations.Results At each time point the tumor weights were (0.31±0.13),(0.61±0.12),(1.43±0.37),(2.38±0.92),(3.74±0.96) and (4.85±1.02) g respectively,the pulmonary metastases rates 0,0,20%,100%,and 100%,respectively,and the serum CK19 levels (4.79±1.16),(5.06±1.21),(8.55±1.25),(40.71±9.87),(76.29±20.00) and (95.94±19.68) μg/L,respectively ( P <0.01).Serum CK19 level was increased parallel with tumor progression and rose significantly when pulmonary metastases occurred.Conclusion The CK19 level in tumor bearing nude mice in increased proportionally with tumor progression,significantly higher in those mice with pulmonary metastasis,implying its potential application as a sensitive indicator for metastasis.