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Targeting a methioninase-containing fusion protein to breast cancer urokinase receptors inhibits growth and migration.
- Source :
-
Anticancer research [Anticancer Res] 2006 May-Jun; Vol. 26 (3A), pp. 1745-51. - Publication Year :
- 2006
-
Abstract
- Background: We previously reported that a novel fusion protein (consisting of an amino-terminal fragment of urokinase which binds to the urokinase receptor, and L-methioninase which depletes methionine and arrests the growth of methionine-dependent tumors) inhibited MCF-7 breast cancer cells in vitro.<br />Materials and Methods: We produced this fusion protein, L-methioninase, and a mutated fusion protein without L-methioninase activity by recombinant methods. MCF-7 cell proliferation and mobility were measured in vitro in a culture wounding assay. Protein binding to MCF-7 cells was measured by immunocytochemical localization. MCF-7 tumor xenograft growth was measured in nude mice.<br />Results: The fusion protein was significantly more effective than L-methioninase in either the in vitro or in vivo assays. The binding assay showed that the unmutated and mutated fusion protein bound to the cells, but L-methioninase did not.<br />Conclusion: Our results suggest that this fusion protein has potential as a therapeutic agent for cancer treatment.
- Subjects :
- Animals
Breast Neoplasms pathology
Carbon-Sulfur Lyases genetics
Cell Growth Processes drug effects
Cell Line, Tumor
Cell Movement drug effects
Humans
Injections, Intralesional
Mice
Mice, Nude
Mutagenesis, Site-Directed
Receptors, Cell Surface genetics
Receptors, Urokinase Plasminogen Activator
Recombinant Fusion Proteins biosynthesis
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Xenograft Model Antitumor Assays
Breast Neoplasms drug therapy
Breast Neoplasms metabolism
Carbon-Sulfur Lyases administration & dosage
Receptors, Cell Surface metabolism
Recombinant Fusion Proteins administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 0250-7005
- Volume :
- 26
- Issue :
- 3A
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 16827102