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.


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.


CONCLUSIONS
Our results suggest that this fusion protein has potential as a selective therapeutic agent for the treatment of various methionine-dependent cancers.
Palwai
Naveen R
NR
Bioengineering Center and the School of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman, Oklahoma 73019, USA.
Zang
Xiao-Ping
XP
Harrison
Roger G
RG
Pento
J Thomas
JT
D013437:Carbon-Sulfur Lyases / Q000235:genetics / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*
C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase