Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvessel density in non-small cell lung cancer.
Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvessel density in non-small cell lung cancer.
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DOI：
10.1186/1471-2407-9-180
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发表时间：
2009-06-11
期刊：
影响因子：
3.8
通讯作者：
Giaccone G
中科院分区：
文献类型：
--
作者：
van Cruijsen H;Ruiz MG;van der Valk P;de Gruijl TD;Giaccone G
肿瘤免疫逃逸和血管生成促进了肿瘤的进展，神经节苷脂和信号转导和转录激活因子(STAT)-3的激活参与了这些过程。由于两者都被认为是新的治疗靶点，我们评估了神经节苷脂GM3表达和STAT3激活与抑制树突状细胞(DC)激活和血管生成在非小细胞肺癌(NSCLC)中的可能联系。应用免疫组织化学方法检测176例非小细胞肺癌组织中N-糖基化GM3(GM3)和磷酸化STAT3(PSTAT3)的表达。以GM3和pSTAT3表达的中位数作为切断点。微血管密度(MVD)测定采用CD34染色和组织学方法。CD1a和CD83分别用于检测未成熟树突状细胞和成熟树突状细胞。94%的NSCLC组织表达GM3，71%的NSCLC组织表达核PSTAT3。中位总生存期为40.0个月。GM3低表达和pSTAT3高表达均与预后不良有关，与GM3差异有统计学意义(P=0.08)。CD34染色和形态学测定的微血管密度(MVD)在GM3高表达的非小细胞肺癌组织中较低。CD1a+细胞(未成熟树突状细胞)在非小细胞肺癌组织中的比例高于瘤周肺组织，而CD83+细胞(成熟树突状细胞)在瘤周肺组织中比例较高。CD83+DC在GM3高表达的非小细胞肺癌组织中较少出现。GM3和pSTAT3在非小细胞肺癌中广泛表达。根据CD83的表达，GM3而不是pSTAT3似乎参与了肿瘤诱导的DC抑制。PSTAT3的表达与MVD无关，而GM3可能具有抗血管生成的作用。
Tumor immune escape and angiogenesis contribute to tumor progression, and gangliosides and activation of signal transducer and activator of transcription (STAT)-3 are implicated in these processes. As both are considered as novel therapeutic targets, we assessed the possible association of ganglioside GM3 expression and STAT3 activation with suppression of dendritic cell (DC) activation and angiogenesis in non-small cell lung cancer (NSCLC). Immunohistochemistry was performed on a tissue array to determine N-glycolyl GM3 (GM3) and phosphorylated STAT3 (pSTAT3) expression in 176 primary NSCLC resections. Median values of GM3 and pSTAT3 expression were used as cut off. Microvessel density (MVD) was determined by CD34 staining and morphology. CD1a and CD83 were used to determine infiltrating immature and mature dendritic cells, respectively. 94% and 71% of the NSCLC samples expressed GM3 and nuclear pSTAT3, respectively. Median overall survival was 40.0 months. Both low GM3 expression and high pSTAT3 expression were associated with a worse survival, which reached near significance for GM3 (P = 0.08). Microvessel density (MVD), determined by CD34 staining and morphology, was lower in NSCLC samples with high GM3 expression. CD1a+ cells (immature DCs) were more frequent in NSCLC tissues as compared to peritumoral lung tissue, while CD83+ cells (mature DCs) were more frequent in peritumoral lung tissue. CD83+ DCs were less frequent in NSCLC tissues with high GM3 expression. GM3 and pSTAT3 are widely expressed in NSCLC. Based on CD83 expression, GM3, but not pSTAT3, appeared to be involved in tumor-induced DC suppression. pSTAT3 expression was not associated with MVD, while GM3 might play an anti-angiogenic role.
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