Suppression of metastasis-associated S100A4 gene expression by gamma-interferon in human colon adenocarcinoma cells.

S100A4 belongs to the S100 subfamily of calcium-binding proteins and has been suggested to be directly involved in invasion and metastasis of rodent and human tumour cells. The present study demonstrates that interferon gamma (IFN-gamma), but not IFN-alpha and IFN-beta, down-regulates the S100A4 mRNA level in colon adenocarcinoma WiDr cells in time- and dose-dependent manners. The effect was not associated with any cytotoxicity and was specific for the S100A4 mRNA, since the levels of the S100A6 and GAPDH mRNAs were not significantly affected by the treatment. IFN-gamma also strongly suppressed the S100A4 mRNA expression in HT-29 cells, but weakly in Colo201 cells. Flow cytometric analysis revealed that the level of the IFN-gamma receptor expression in Colo201 cells was lower than that in WiDr and HT-29 cells, suggesting that the suppression of the S100A4 expression by IFN-gamma depends on the amount of cell surface IFN-gamma receptor protein. IFN-gamma had no effect on the transcription rate of the S100A4 gene but reduced the stability of the S100A4 mRNA. WiDr cells treated with IFN-gamma showed reduced motile ability, further supporting the assumption that the S100A4 gene product is involved in controlling cell motility.