[Function of IL-18 in promoting metastasis of lung cancer].
OBJECTIVE
To study the function of IL-18 in promoting metastasis of lung cancer.


METHODS
The differential expression of IL-18 protein or mRNA level between highly and poorly metastatic sublines of human lung giant cell carcinoma metastatic model was detected by Western blot, semi-quantitative RT-PCR and northern blot analysis. The poorly metastatic PLA801C subline or highly metastatic PLA801D subline was transfected with constructed IL-18 sense or IL-18 antisense expressed plasmid by lipofectamine stable transfection technique. The metastasis-related effect mediated by IL-18, the metastatic phenotype differences, cell motility and cell invasion potential in vitro determined by MICS system and the expression level of metastasis-associated biomarkers detected by Western blot analysis, were compared between IL-18 stably transfectants and mock control, i.e. between PLA801C/IL-18(S) and PLA801C/pcDNA3.1, or between PLA801D/IL-18(As) and PLA801D/pcDNA3.


RESULTS
IL-18 was only present in highly metastatic PLA801D subline at either protein or mRNA level, which implied that IL-18 might play a role in promoting metastasis of lung cancer. After IL-18 sense expressed plasmid was transfected into poorly metastatic PLA801C subline, IL-18 fused protein with myc tag detected by Western blot analysis using either IL-18 or myc tag monoclonal antibody. In addition, cell motility ability in vitro was significantly increased about 3 times and E-cadherin protein was significantly down-regulated at about 50% in PLA801C/IL-18(S) transfectants compared with mock control. While IL-18 expressed plasmid was transfected into highly metastatic PLA801D subline, IL-18 protein and mRNA were simultaneously decreased by 30%. In addition, cell invasion ability in vitro was significantly decreased at about 75% and E-cadherin protein was significantly up-regulated in PLA801D/IL-18(As) transfectants compared with mock control.


CONCLUSIONS
IL-18 might play a role in enhancing tumor metastasis of lung cancer by down-regulating E-cadherin protein expression.
Jiang
Dai-feng
DF
Department of Genomics & Proteomics, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Liu
Wan-li
WL
Lu
Ying-lin
YL
Qiu
Zong-yin
ZY
He
Fu-chu
FC
D015820:Cadherins / Q000378:metabolism; D018286:Carcinoma, Giant Cell / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement; D016373:DNA, Antisense / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics; D010957:Plasmids; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D015820:Cadherins; D016373:DNA, Antisense; D020382:Interleukin-18; D012333:RNA, Messenger