Effect of alpha 1-Acid glycoprotein expressed in cancer cells on malignantcharacteristics

The alpha1-acid glycoprotein (AAG) is a prototypical serum acute phase reac tant in most mammalian species; it is synthesized mainly in liver parenchym al cells. Recently, we found that mRNAs of AAG were expressed in non-hepati c cancer cells, and the expression levels were regulated by the cytokines - IL-1, IL-6, and TNF alpha. The functional role of AAG in non-hepatic cance r cells has not yet been established. In order to understand the functional role of the AAG expressed in HT-29 cells, the cancer cells were transfecte d with cloned cDNA for AAG, or exposed to antisense oligodeoxynucleotide (O DN) for AAG, The colony-forming capacity, invasion, and adhesion to laminin of these transformed cancer cells were measured. Overexpression of AAG by transfection, and inhibition of the AAG expression by antisense ODNs were i dentified by Western blot as well as nested reverse transcriptase-polymeras e chain reaction (nested RT-PCR), respectively. Results showed that the ove rexpression of AAG by transfection reduced colony-forming capacities, invas ion, and adhesion to laminin of the cancer cells; on the other hand, the an tisense ODN for AAG elevated colony-forming capacities, invasion, and adhes ion to laminin of the cancer cells. These results suggest that AAG, express ed in cancer cells inhibited proliferation, invasion, and metastasis of the cancer cells.