S100A4 antisense oligodeoxynucleotide suppresses invasive potential of neuroblastoma cells.
BACKGROUND
S100A4 gene product has been implicated in tumor invasion and metastasis. The overall survival rate of children with neuroblastoma remains poor because of disease dissemination at the time of diagnosis. The purpose of this study was to investigate the effect and mechanism of S100A4 on invasion and metastasis of neuroblastoma.


METHODS
A 20-mer phosphorothioate antisense oligodeoxynucleotide (asODN) targeted against the S100A4 mRNA was transfected into the human neuroblastoma cell line LA-N-6 by Lipofectamine 2000. The expressions of S100A4 and MMP-2 mRNAs were quantified by the reverse transcription polymerase chain reaction. The capability of migration and invasion of LA-N-6 cells were evaluated by the transwell chamber assay.


RESULTS
The S100A4 mRNA and the MMP-2 mRNA levels in asODN-treated cells were decreased by 35.6% and 25.5%, respectively, compared with those in nontreated cells. The numbers of migrating and invading LA-N-6 cells were both significantly lower in the asODN-treated groups than those in the nontreated groups ( 9.33 +/- 4.73 vs 20.67 +/- 2.89 and 2.33 +/- 1.15 vs 9.00 +/- 2.65, respectively; both P = .03 ).


CONCLUSIONS
The S100A4 asODN significantly reduced the S100A4 mRNA levels and the motility and invasive ability of neuroblastoma cells, with concomitant decrease of the MMP-2 mRNA levels. Thus, S100A4 may exert its effect on invasion and metastasis of neuroblastoma cells by stimulating the motility of tumor cells as well as influencing the expression of MMP-2.
Gao
Xiao-ning
XN
Department of Pediatrics, General Hospital of PLA, Beijing, PR China.
Tang
Suo-qin
SQ
Zhang
Xiao-fei
XF
D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000473:pathology*; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics* / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D020778:Matrix Metalloproteinase 2