肿瘤相关成纤维细胞自噬促进肺腺癌细胞侵袭迁移

Autophagy in cancer associated fibroblasts promotes lung adenocarcinoma cells migration and invasion

目的肿瘤细胞自噬与肿瘤发生、发展密切相关,但肿瘤微环境细胞自噬与肿瘤的关系尚不清楚.肿瘤相关成纤维细胞(CAFs)是肿瘤微环境的重要组成部分,可分泌细胞因子促进肿瘤侵袭转移.本研究旨在探讨CAFs自噬对肺腺癌侵袭迁移的影响.方法以肺腺癌细胞株A549和CAFs进行非接触共培养为实验组,单独培养的A549为对照组,观察CAFs过表达自噬核心基因自噬相关基因5(ATG5)及CAFs对照组对A549侵袭迁移的影响.酶联免疫吸附试验检测培养上清白细胞介素-6、及白细胞介素-8表达水平.应用SPSS 23.0统计软件分析,计量资料采用均值±标准差(Mean±SD),两组间样本均数比较采用t检验;多组间两两样本均数比较采用方差分析.结果与单独培养的A549比较,CAFs共培养后A549侵袭[(54.6±8.6)个/cm^2比(124.3±19.6)个/cm^2]迁移能力[(57.0±10.5)个/cm^2比(122.7±17.6)个/cm^2]增强,而与过表达ATG5的CAFs共培养后,A549侵袭[(124.3±19.6)个/cm^2比(280.0±32.1)个/cm^2]迁移能力[(122.7±17.6)个/cm^2比(269.3±72.7)个/cm^2]进一步增强,差异有统计学意义(F=18.640、80.630,P<0.05).过表达ATG5后CAFs分泌的IL-6[(545.5±28.2)ng/L比(865.4±70.9)ng/L]和IL-8[(374.2±62.2)ng/L比(672.4±24.2)ng/L]明显增高,差异有统计学意义(t=7.261、7.738,P<0.05).结论CAFs自噬可通过分泌IL-6/IL-8促进肺腺癌细胞侵袭迁移.

Objective Autophagy is a process by which cellular material is delivered to lysosomes for degradation,providing energy and macromolecular precursors.Cancer-associated fibroblasts(CAFs)have an important role in reprogramming the tumor microenvironment,and exhibit enhanced migratory capacity through autocrine and paracrine.This study aims to explore the possible effects of CAFs autophagy on lung adenocarcinoma cells migration and invasion.Methods Lung adenocarcinoma cell line A549 was co-cultured with or without CAFs via Transwell and Matrige lassay under the same culture condition,the effects of CAFs autophagy on the migration and invasion of A549 were observed.Results We demonstrate autophagy activated CAFs have great ability than CAFs to enhance the migration[(122.7±17.6)cells/cm^2 vs.(269.3±72.7)cells/cm^2]and invasion[(124.3±19.6)cells/cm^2 vs.(280.0±32.1)cells/cm^2]of lung adenocarcinoma(LUAD)cell line(F=18.640,80.630,P<0.05).Interleukin 6[(545.5±28.2)ng/L vs.(865.4±70.9)ng/L]and interleukin 8[(374.2±62.2)ng/L vs.(672.4±24.2)ng/L]were highly expressed in the autophagy activated CAFs conditioned media(t=7.261,7.738,P<0.05).Conclusion Our results establish an oncogenic function for secretory autophagy in CAFs that promote LUAD migration and invasion.