恶性黑色素瘤调节肺组织微环境并促进肿瘤肺转移的实验研究  

Primary tumor regulates the pulmonary microenvironment in melanoma carcinoma model and facilitates lung metastasis

作　　者：袁冰[1] 李冉冉[1] 韩明勇[1] 

机构地区：[1]山东大学附属省立医院东院保健综合(肿瘤)科,山东济南250014

出　　处：《山东大学学报（医学版）》2016年第11期13-18,共6页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81272351)

摘　　要：目的探讨转移前期原发黑色素瘤对肺组织微环境的作用及其对转移的影响。方法将黑色素瘤细胞B16种植于雌性Balb/c小鼠背部,建立荷瘤小鼠动物模型;通过小鼠尾静脉注射B16细胞建立转移模型;塞来昔布灌胃处理小鼠建立抗炎治疗模型。采用肺组织干湿比和HE染色分析肺组织炎症反应,应用ELISA试剂盒检测血清及细胞培养上清液中的细胞因子水平。结果在转移前期,与对照组小鼠相比,实验组荷瘤小鼠肺组织明显水肿,肺干湿比明显升高,两组相比差异有统计学意义(P<0.001);同时发现B16细胞易于出现在肺组织炎症细胞聚集的部位。ELISA检测结果显示,与对照组相比,实验组荷瘤小鼠血清VEGF、M-CSF和TNF-α含量明显升高,两组相比差异有统计学意义(P<0.001)。B16培养上清可以显著诱导肺组织炎症反应,与对照组相比,实验组小鼠肺组织转移瘤显著增多(P<0.001);给予抗炎药物塞来昔布处理后,与对照组相比,实验组小鼠肺组织炎症反应明显下降,肺转移瘤数目明显减少(P=0.005)。结论在肿瘤转移前期,原发恶性黑色素瘤能够调节肺组织微环境,诱导肺组织炎症反应并促进肺转移;塞来昔布可缓解肺组织炎症反应并抑制肺转移。Objective To explore the effect of primary melanoma on lung microenvironment and metastasis. Methods Melanoma cells（B16） were implanted into the back of Balb / c mice to build tumor-bearing mice model. Metastatic model was established by injecting B16 into the caudal vein of mice intravenously,and anti-inflammatory treatment of celecoxib was applied by gavage. Pulmonary inflammation response was analyzed by wet / dry ratios and HE staining,the circulating levels of proinflammatory cytokines in sera were evaluated by ELISA. Results In the premetastatic phase,there was a significant increase in edema and lung wet / dry ratio in experimental group compared to the control group（P 〈 0. 001）. HE staining showed that a large number of inflammatory cells aggregated in the lungs of experimental group. Tumor cells tended to metastasize to where the inflammatory cells invaded. ELISA showed that compared with the control group,there was a significant increase in the levels of VEGF,M-CSF and TNF-α in the experimental group. B16 conditioned media induced inflammation cells infiltrate in lung tissues,and the number of metastatic foci in lungs lesions was higher in the experimental group than that in the control group（P 〈 0. 001）. There was a significant decrease in edema,lung wet / dry ratio,and inflammation cells infiltration in the experimental group compared to thecontrol group（P = 0. 005）. Conclusion In the premetastatic phase,the melanoma induces pulmonary inflammation response,changes the lung environment and then facilitates lung metastasis. Applying of celecoxib can inhibit lung inflammation and prevent lung metastasis.

关 键 词：黑色素瘤 肺 炎症 微环境 肿瘤转移 细胞因子 

分 类 号：R73-37[医药卫生—肿瘤]