摘要
目的探讨甲酰肽受体1(formyl peptide receptor 1,FPR1)在肺腺癌组织中的表达以及对肺腺癌细胞迁移、成瘤能力的影响。方法采用免疫组化法检测肺腺癌组织及癌旁组织中FPR1的表达,分析患者临床资料的相关性。采用人肺腺癌细胞A549为分析对象,检测FPR1激动剂甲酰甲硫氨酰(N-formyl methionyl leucyl phenylalanine,f MLP)以及拮抗剂Boc2对细胞迁移的影响;构建裸鼠皮下成瘤模型,绘制肿瘤生长曲线; 2周后处死全部裸鼠,比较各组裸鼠肿瘤平均质量;应用酶联免疫吸附反应(enzyme-linked immunosorbent assay,ELISA)检测各组裸鼠血清中血管内皮生长因子-C(vascular endothelial growth factorC,VEGF-C)的表达水平;应用Western blot检测各组细胞中FPR1、ERK蛋白活性以及各组裸鼠肿瘤中FPR1蛋白的表达变化。结果 50例肺腺癌癌组织中FPR1阳性率为68%(34/50),与肺腺癌TNM分期显著相关;与患者年龄、性别、吸烟史无相关性。与对照组相比,f MLP能显著促进癌细胞的迁移能力、促进FPR1和p-ERK1/2蛋白表达(P均<0. 01),而Boc2则抑制了该作用(P均<0. 01)。与模型组相比,f MLP能促进肿瘤的生长及肿瘤中FPR1、血清中VEGF-C的水平(P均<0. 01),而Boc2则对该效果起抑制作用(P均<0. 05)。结论 f MLP能通过上调FPR1表达促进人肺腺癌细胞的迁移和成瘤能力,可能与ERK信号通路的激活有关及VEGF-C的分泌调控相关;且FPR1的阳性与肺腺癌TNM分期呈显著相关性,提示FPR1表达可能与肺腺癌的发生、发展密切相关。
Purpose To determinate the expression of formyl peptide receptor 1(FPR1)in cancer tissues of patients with lung adenocarcinoma and its effect on migration and the tumorigenic ability of human lung adenocarcinoma cells.Methods The expression of FPR1 in cancer tissues and adjacent tissues of lung adenocarcinoma patients was detected by immunohistochemistry,and the correlation analysis was conducted with the patient’s clinical data.In addition,the effect of FPR1 agonist and antagonist on cell migration was investigated by using human lung adenocarcinoma cell A549.And then,subcutaneous tumorigenesis models were established and the tumor growth curves were drawn.After 2 weeks,all nude mice were sacrificed and the average quality of the tumors in each group of nude micewas compared.The levels of vascular endothelial growth factor-C(VEGF-C)in serum of nude mice were detected by enzyme-linked immunosorbent assay(ELISA).The activity of FPR1 and ERK protein in cells in each group andthe expression of FPR1 protein in each group of nude mice tumors were detected by Western blot.Results The positive rate of FPR1 was 68%(34/50)in cancer tissuesof 50 patientswith lung adenocarcinoma,and it was significantlyrelated with the TNM staging of lung adenocarcinoma,but not correlated with age,sex and smoking history.N-formylmethionylleucylphenylalanine(fMLP)significantly promoted the migration of cancer cells,and promoted the expression of FPR1 and p-ERK1/2 protein(all P<0.01),while Boc2 inhibited this effect(all P<0.01).Compared with the model group,fMLP promoted the growth of tumor and levels of FPR1 in tumor and VEGF in serum(all P<0.01),while Boc2 inhibited this effect(all P<0.05).Conclusion fMLP can promote the migration and tumorigenicity of human lung ade-nocarcinoma cells by up-regulating the expression of FPR1,which may be related to the activation of ERK signaling pathway and the regulation of VEGF-C secretion by FPR1.And the positive expression of FPR1 is significantly correlated with the TNM stage of lung adenocarcinoma.These results suggest that the expression of FPR1 may be closely related to the occurrence and development of lung adenocarcinoma.
作者
黄波
郭红荣
丁洁
王红娟
徐建群
HUANG Bo;GUO Hong-rong;DING Jie;WANG Hong-juan;XU Jian-qun(Department of Respiratory Medicine,Tongren Hospital of Wuhan University/Wuhan Third Hospital,Wuhan 430070,China;Department of Nephrology,Tongren Hospital of Wuhan University/Wuhan Third Hospital,Wuhan 430070,China)
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2018年第10期1104-1109,共6页
Chinese Journal of Clinical and Experimental Pathology
基金
武汉市卫生计生委科研基金(WX16D11)
关键词
肺肿瘤
腺癌
甲酰肽受体1
迁移
成瘤能力
lung neplasms
adenocarcinoma
formyl peptide receptor 1
migration
tumorigenic ability
