免疫球蛋白样转录子2在胃癌细胞中的表达及临床意义

Expression and clinical significance of immunoglobulin-like transcript 2 in gastric cancer cells

目的检测免疫球蛋白样转录子2(ILT2)在胃癌组织及胃癌细胞系中的表达,分析其表达与胃癌生物学行为和临床特征的关系。方法采用免疫组织化学方法检测50例胃癌病理组织中ILT2蛋白的表达,并结合临床病理指标进行分析。采用实时荧光定量PCR和FACS流式细胞术检测6株高(MKN1)、中(SGC-7901,AGS)、低(MGC-803)及未分化(HGC-27,BCG-823)人胃癌细胞株ILT2的mRNA和蛋白表达。MTT法检测自然杀伤细胞(NK-92)和外周血淋巴细胞(PBMCs)对HGC-27、MKN1两种胃癌细胞的杀伤活性。结果 50例胃癌病理组织中ILT2表达阳性率为62.0%(31/50),正常胃组织不表达ILT2。在低分化型胃癌组织中ILT2表达阳性率为73.3%(22/30),在分化型组织中表达阳性率为45%(9/20),差异有统计学意义(χ2=4.089,P<0.05);肿瘤直径>5 cm时胃癌组织中ILT2表达阳性率为84.2%(16/19),明显高于肿瘤<5 cm时患者阳性率48.4%(15/31),差异有统计学意义(χ2=6.417,P<0.01)。6株人胃癌细胞均表达ILT2,ILT2在低分化和未分化胃癌细胞中表达阳性率高于中分化和高分化细胞(P<0.05)。在不同效靶比下人PBMC及NK-92细胞对MKN1细胞(ILT2低表达)的杀伤能力高于对HGC-27细胞(ILT2高表达)的杀伤(P<0.05)。结论胃癌组织细胞ILT2的表达与细胞分化程度和胃癌临床病理特征显著相关,PBMC和NK-92细胞对高表达ILT2的胃癌细胞的杀伤能力降低。提示ILT2可能参与肿瘤的免疫逃逸并可作为胃癌诊断和治疗的新靶点。

Objective To investigate expression of immunoglobulin-like transcript 2（ILT2） and its relationship with biological behavior and clinicopathoiogical features in gastric carcinoma tissues and cell lines.Methods Expression of the ILT2 protein was detected by the immunohistochemical SP method in 50 cases of gastric tissues.Correlations of expression of the ILT2 protein with clinicopathoiogical features were analyzed.Protein and mRNA expressions of ILT2 in 6 gastric cancer cell lines with diverse differentiation（highly differentiated,MKN1;moderately differentiated,SGC-7901 and AGS;lowly differentiated,MGC-803;undifferentiated,HGC-27 and BCG-823） were analyzed by Real-time fluorescent quantitative PCR and FACS flow cytometry.Cytolytic activities of freshly isolated PBMC cells and NK-92 cells against MKN1 and HGC-27 were determined by MTT assay.Results Expression of ILT2 was higher in gastric cancer tissues（31/50,62.0%）,while there was no ILT2 expression in normal gastric tissues.Expression of ILT2 was significantly higher in poorly differentiated cancer tissues（22/30,73.3%） than in well-differentiated tissues（9/20,45%）（χ2=4.089,P0.05）.Also,expression of ILT2 was significantly higher in bigger tumor size with D5 cm（16/19,84.2%） than in smaller tumor size with D5 cm（15/31,48.4%）（χ2=6.417,P0.01）.ILT2 mRNA and protein were differently expressed in all the 6 gastric cancer cell lines,and lowly differentiated and undifferentiated gastric cancer cell lines had higher ILT2 expression than moderately and highly differentiated cell lines（P0.05）.Cytolytic activities of PBMC and NK-92 cells against ILT2high HGC-27 cells were lower than those against ILT2low MKN1 cells in different effector-target ratios（P0.05）.Conclusion The inhibitory receptor ILT2 is expressed in gastric carcinoma and its expression level is related to differentiation stage and clinicopathoiogical features.PBMCs and NK-92 cells show lower cytolytic activity against ILT2high gastric cancer cells.ILT2 may be involved in tumor escape and is expected to become a new target to diagnose and treat gastric cancer.