Influence of L-methioninase targeted to the urokinase receptor on the proliferation and motility of lung and prostate cancer cells.

BACKGROUND

Previously, we reported that a novel fusion protein consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase inhibited MCF-7 breast cancer cells in vitro to a greater extent than treatment with L-methioninase.

MATERIALS AND METHODS

The fusion protein, L-methioninase and a mutated fusion protein without L-methioninase activity were produced by recombinant methods. The effects of fusion protein, L-methioninase, and mutated fusion protein treatment on the proliferation and motility of SK-LU-i lung and PC-3 prostate and cancer cells were measured in vitro using a culture wounding assay.

RESULTS

The fusion protein produced a dose-dependent inhibition of the proliferation and motility of both cancer cell lines. In addition, the fusion protein was found to be significantly more effective than L-methioninase alone or mutated fusion protein.

CONCLUSION

Our results suggest that this fusion protein has potential as a selective therapeutic agent for the treatment of various methionine-dependent cancers.