小鼠黑色素瘤肺转移过程中肿瘤细胞出血管的分子机制研究  

The Molecular Mechanism of Extravasation in Mouse Melanoma Lung Metastasis Model

作　　者：逄路明[1,2] 赵成建[2] 赵玉伟[2] 李知勉[2] 杨寒朔[2] 魏于全[2] 

机构地区：[1]四川大学生命科学学院,成都610064 [2]四川大学华西医院生物治疗国家重点实验室,成都610041

出　　处：《四川大学学报（医学版）》2011年第5期594-598,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家973计划(项目编号2004CB518800)资助

摘　　要：目的研究小鼠黑色素瘤细胞肺转移早期肿瘤细胞出血管的分子机制。方法建立稳定表达红色荧光蛋白的小鼠黑色素瘤细胞株B16-RED,并鉴定其增殖和转移能力与B16细胞的异同。构建肺转移模型后48 h和72 h,用荧光标记血管,确定B16-RED细胞出血管的时间。建模后48 h取模型小鼠与正常小鼠肺组织进行32K小鼠全基因组表达芯片分析。结果 B16-RED与B16在细胞形态、增殖能力和肺转移能力等方面无明显差异。建模后48 h内有52.7%的B16-RED细胞完成出血管过程。B16-RED细胞在肺组织出血管过程中肺组织变化的信号通路包括白细胞跨内皮迁移通路、MAPK信号通路等。结论 B16-RED细胞的肺转移出血管是一个复杂的、多步骤的生物学过程,肺组织内有多条重要的信号通路参与此过程。Objective To study molecular mechanisms underlying the extravasation of mice melanoma cells during lung metastasis.Methods B16-RED melanoma cell line was established which stably express the red fluorescent protein.B16-RED cells were compared with B16 cells in ability of proliferation and lung metastasis.A mouse lung metastasis model was established with B16-RED melanoma cells.FITC-dextran was injected i.v.and CD31 indirect immunoflourescence（IIF） staining was made to identify the location of the tumor cells and the time of tumor cell extravasation.Finally,at 48 hours post cell injection,the lung and a normal lung were removed and used for 32K mice microarray analysis.Results B16-RED was consistent with B16 in cell shape and ability of proliferation and lung metastasis.52.7% of B16-RED melanoma cells completed the extravasation within 48 hours in mouse lung metastasis model.Many important signal pathways were involved during lung metastasis, including leukocyte transendothelial migration,MAPK signaling pathway,neuroactive ligand-receptor interaction,focal adhesion,cytokine-cytokine receptor interaction,regulation of actin cytoskeleton,axon guidance,calcium signaling pathway,tight junction,etc.Conclusion The extravasation during metastasis is a complex and multiple-steps process,in which many important signal pathways in host tissues were involved.

关 键 词：黑色素瘤 肺转移 出血管 全基因芯片分析 

分 类 号：R739.5[医药卫生—肿瘤]