CXCR4阳性Lewis肺癌细胞的高致瘤性和高转移潜能  

Highly tumorigenic and metastatic potential of CXCR4 positive cells from Lewis lung carcinoma cell line

作　　者：辇伟奇[1] 敖绪军[2] 陈芳琳[1] 陈正堂[1] 

机构地区：[1]第三军医大学新桥医院全军肿瘤诊治研究所,重庆400037 [2]解放军第532医院普通外科,安徽黄山45041

出　　处：《第三军医大学学报》2010年第4期315-318,共4页Journal of Third Military Medical University

基　　金：国家高技术研究发展计划(863计划;2007AA02Z129);国家自然科学基金(30901790);重庆市自然科学基金(CSTC200BB5117)~~

摘　　要：目的从小鼠肺腺癌细胞株(lewis lung carcinoma,LLC)中分离并鉴定具有高转移潜能的肿瘤干细胞样细胞亚群。方法流式分析Sca1、CXCR4双阳性细胞比例,激光共聚焦检测小鼠肺癌组织中双阳性细胞表达情况;以CXCR4作为磁珠分选细胞的表面标志,检测分选前后细胞活性,观察分析CXCR4阳性亚群的恶性生物学行为。结果LLC细胞中Sca-1、CXCR4双阳性细胞比例为0.1%,CXCR4阳性细胞为0.18%,小鼠肺癌组织存在荧光双染色细胞;分选前细胞活性为(95.58±0.87)%,分选后活力为(94.96±0.76)%(P>0.05);CXCR4阳性亚群在无血清中呈球状生长,CXCR阴性亚群1×105即不可成瘤,CXCR4阳性亚群在7×103仍可成瘤;CXCR4阴性和阳性亚群分别以5×105、2×104密度各接种3只小鼠,前者无转移,而后者2只发生肺转移,1只发生耳转移。结论Lewis肺癌细胞中的CXCR4阳性亚群具有一定的自我更新和转移能力,具备癌转移性干细胞某些特性。Objective To isolate and identify the subgroups of tumor stem-like cells with a highly metastatic potential from Lewis lung cancer （LLC） cell line. Methods The ratio of Sca-1 and CXCR4 cells with dual-color immunofluorescent staining in LLC was determined by flow cytometry, and their expression in lung tissue of mice was detected by laser confocal microscopy. CXCR4^ ＋ cells were used as a magnetic head in isolation of surface markers on the cells as well as in detection of cell activity before and after isolation. Biological behaviors of subgroups of positive CXCR4 cells were observed and analyzed. Results The ratio of Sca-1 and CXCR4^＋ cells in LLC was 0.1% , and the rate of positive CXCR4^＋ cells in LLC was 0.18%. Dual-color immunofluorescence-stained cells were observed in mouse lung tissues. The cell activity was （95.58± 0.87 ） % and （ 94.96 ± 0.76） % respectively, before and after isolation （ P 〉 0. 05 ）. Tumor formation was found in subgroups of positive CXCR4 cells （7× 10^3）. Negative and positive CXCR cells were inoculated into 3 mice respectively at the concentration of 5 × 10^5 and 2 × 10^4 cells. No metastasis occurred in the former group. However, lung metastasis was found in 2 mice and ear metastasis was observed in l mouse of the latter group. Conclusion Subgroups of positive CXCR4 cells in LLC are characterized by certain properties of cancer metastatic stem cells and have the ability to renew themselves and metabolize.

关 键 词：细胞系 肿瘤 癌 非小细胞肺 肿瘤干细胞 小鼠 近交C578L 癌 Lewis肺 受体 CXCR4 

分 类 号：R73-37[医药卫生—肿瘤] R730.23[医药卫生—临床医学]