GDNF对唾液腺腺样囊性癌嗜神经侵袭中基质降解和黏附能力的影响

The effect of GDNF on matrix-degrading and cell-adhesion during perineural invasion of salivary adenoid cystic carcinoma

目的:探讨GDNF对唾液腺腺样囊性癌(adenoma cystic carcinoma,ACC)嗜神经侵袭(perineural invasion,PNI)中基质降解和黏附能力变化的影响。方法:应用免疫组织化学染色SP法对42例ACC和5例正常唾液腺组织中GDNF、MMP-9、NF-κB、整合素β1的表达进行检测。采用SPSS16.0软件包对数据进行统计学分析。结果 :GDNF在ACC肿瘤细胞的细胞质和肿瘤周围的神经纤维中呈阳性表达。NF-κB、MMP-9、整合素β1在ACC肿瘤细胞的细胞质均呈阳性表达,且可见NF-κB表达于细胞核,整合素β1表达于细胞膜,阳性表达率分别为69.05%(29/42)、66.67%(28/42)和61.90%(26/42)。NF-κB、MMP-9、整合素β1的表达在PNI组和非PNI组间差异显著,P值分别为0.005、0.011、0.001。GDNF与NF-κB、MMP-9、整合素β1表达呈正相关,r=0.443,P=0.003;r=0.401,P=0.009;r=0.535,P=0.000。MMP-9、整合素β1与NF-κB表达呈正相关,r=0.501,P=0.001;r=0.429,P=0.005。MMP-9的表达与整合素β1表达呈正相关,r=0.381,P=0.013。结论 :GDNF在ACC嗜神经侵袭中促进基质降解和黏附能力改变。NF-κB、MMP-9、整合素β1的表达与GDNF关系密切,共同促使ACC神经侵袭的发生与进展。

PURPOSE： To investigate the possible contribution of GDNF in matrix-degrading, cell-adhesion during perineural invasion（PNI） of salivary adenoid cystic carcinoma（ACC）. METHODS： Totally 42 ACCs and 5 normal salivary tissues were included in the present study.Immunohistochemical staining SP method was used to detect the expression of GDNF,MMP-9,NF-κB,integrin β1 in ACC specimens and normal salivary tissues. Statistical analysis was performed using SPSS16.0 software package. RESULTS：GDNF was strongly expressed in ACC tumor cells and nerve fibers adjacent to ACC tumor cells. NF-κB, MMP-9, integrin β1 were positively expressed in ACC cell cytoplasm,integrin β1 was also found in ACC cell membrane, and NF-κB in nuclei occasionally. The positive expression rate was69.05%（29/42）,66.67%（28/42）,61.90%（26/42）, respectively. The differences between the expression of NF-κB, MMP-9,integrinβ1 in PNI group and non-PNI group were significant（P=0.005,P=0.011,P=0.001, respectively）. Expression of NF-κB, MMP-9, integrin β1 was correlated to that of GDNF（r =0.443, P =0.003; r =0.401, P =0.009; r =0.535, P =0.000,respectively）. Expression of MMP-9 and integrin β1 was positively correlated to that of NF-κB（r=0.501, P=0.001; r=0.429,P=0.005）. Expression of MMP-9 was correlated positively to that of integrin β1（r=0.381, P=0.013）. CONCLUSIONS：GDNF may increase the matrix-degrading and cell-adhesion of ACC in the process of PNI. NF-κB, MMP-9 and integrinβ1 involve in ACC cells invading nerves.