Lewis肺癌在小鼠体内传代过程中生长转移能力的演变与炎症的关系
Relation between inflammation and growth and metastasis of Lewis lung carcinoma in process of serial passage in mice
卞俊杰 1郭伟华 1张艳芳 1董伯升 1李醒亚1
作者信息
- 1. 李醒亚,郑州大学第一附属医院肿瘤科,河南,郑州,450052
- 折叠
摘要
目的:观察Lewis肺癌细胞株(LLC)在C57/BL6小鼠体内连续传代过程中其生长转移能力及瘤组织中炎性因素的变化,探讨肿瘤生长转移能力的演变与炎症的关系.方法:将LLC细胞接种于C57/BL6小鼠腋下,建立第1代荷瘤鼠模型,荷瘤鼠连续传代,于第2,8,15代各传15只小鼠分为早期、中期、晚期组,观察3组小鼠的出瘤速度及肺转移情况.免疫组化法检测3组瘤组织中巨噬细胞密度、微血管密度(MVD)、核转录因子-κB(NF-κB)、基质金属蛋白酶-9(MMP-9)的表达情况.结果:随着荷瘤鼠传代次数的增加肿瘤的生长转移能力逐渐增强,早期、中期、晚期3组小鼠的出瘤速度明显加快;肺转移率明显增加,分别为13%,60%,100%(P<0.01).早期、中期、晚期3组小鼠瘤组织中浸润的巨噬细胞分别为(24.87±8.54),(36.33±10.02),(47.20±13.49)个/HP;微血管密度分别为(24.73±10.38),(41.27±13.50),(55.80±21.31)个/HP;NF-κB,MMP-9的表达明显增强,差异具有统计学意义(P<0.05).肿瘤组织中MVD,NF-κB,MMP-9的表达均与巨噬细胞的增多呈正相关,差异具有统计学意义(P<0.01).结论:Lewis肺癌在小鼠体内连续传代过程中生长转移能力逐渐增强,这种演变与肿瘤组织中炎症浸润的增强有重要的关系.
Abstract
AIM: To observe the changes of neoplastic growth and metastasis and the variation of inflammation in neoplasm in the serial passage of tumor-bearing mice and to discuss the correlation between the variations of tumor biological characters in vivo and inflammation. METHODS: Lewis lung tumor cells were inoculated subcutaneously into C57/BL6 mice and the first generation of tumor bearing mice was established. The tumor bearing mice were then serially passaged. Forty-five mice were inoculated on the second generation (the early group),the eighth generation (the intermediate group) and the fifteenth generation (the late group),with 15 mice in each group. To observe the time of onco-genesis and the rate of pulmonary metastasis,immunohistochemis-try was used to detect the density of macrophages,the microvessel density (MVD),the expressions of nuclear factor-kappa B ( NF-κB ) and matrix metalloproteinase-9 ( MMP-9) in neoplasm in each group. RESULTS: Oncogenesis was speeded up in the 3 groups with the increasing times of passages( P < 0.01). The rate of lung metastasis increased significantly ( P < 0. 01 ) and the rate of pulmonary metastasis in the early,intermediate and late groups was 13.3%,60% and 100%,respectively. The density of mae-rophage and the microvessel density (MVD) in the 3 groups was respectively (24.87 ± 8. 54),(36. 33 ± 10. 02) and (47. 20 ± 13.49),and (24.73 ± 10.38),(41.27 ±13. 50)and (55.80± 21.31),with significant difference (P < 0. 01,both). The expression of NF-κB and MMP-9 in neoplasm gradually increased (P<0. 01) and the expression of CD31,NF-κB and MMP-9 were positively correlated to the density of macrophage in peo-plasm( P < 0. 01). CONCLUSION: The growth and metastasis of Lewis lung carcinoma gradually enhance in the process of serial passage in miee and the dynamic variations are correlated with the inflammation in neoplasm.
关键词
癌/Lewis肺/转移/演变/炎症/巨噬细胞Key words
carcinoma,Lewis lung/metastasis/variation/inflammation/macrophage引用本文复制引用
出版年
2009