Expression of antisense RNA to S100A4 gene encoding an S100-related calcium-binding protein suppresses metastatic potential of high-metastatic Lewis lung carcinoma cells.
S100A4 (also known as pEL98/mts1/p9Ka/18A2/42A/calvasculin /FSP1/CAPL), a member of S100-related calcium-binding proteins, has been implicated to play a role in metastasis. In the present study, we examined the effect of antisense S100A4 RNA on metastatic potential of Lewis lung carcinoma (LLC) cells. High-metastatic All cells were transfected with the expression vector containing S100A4 cDNA in an inverted (antisense) orientation under the transcriptional control of the mouse metallothionein promoter. Treatment of a stably transfected clone (AS10 cells) with Zn2+ resulted in the suppression of the experimental metastatic ability, which was accompanied with the expression of antisense S100A4 RNA and the suppression of the S100A4 expression at both the mRNA and the protein levels. To further confirm the effect of antisense S100A4 RNA, we established several clones after retroviral transduction with an antisense S100A4 construct. Notably, reduced metastatic potential was also evident in these clones. In the antisense S100A4 RNA-expressing cells, cell motility and in vitro invasiveness were found to be suppressed.
Takenaga
K
K
Division of Chemotherapy, Chiba Cancer Center Research Institute, Chuoh-ku, Chiba, Japan.
Nakamura
Y
Y
Sakiyama
S
S
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D005822:Genetic Vectors; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000378:metabolism*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D014162:Transfection; D015032:Zinc / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D016372:RNA, Antisense; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D015032:Zinc