PMID- 18628476
OWN - NLM
STAT- MEDLINE
DCOM- 20080916
LR  - 20091119
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 14
DP  - 2008 Jul 15
TI  - A novel recombinant soluble splice variant of Met is a potent antagonist of the 
      hepatocyte growth factor/scatter factor-Met pathway.
PG  - 4612-21
LID - 10.1158/1078-0432.CCR-08-0108 [doi]
AB  - PURPOSE: The Met receptor tyrosine kinase and its ligand, hepatocyte growth 
      factor/scatter factor (HGF/SF), are involved in a wide range of biological 
      activities, including cell proliferation, motility, invasion, and angiogenesis. 
      The HGF/SF-Met signaling pathway is frequently activated in a variety of cancers, 
      and uncontrolled Met activation correlates with highly invasive tumors and poor 
      prognosis. In this study, we investigated the inhibitory effect of a novel 
      soluble splice variant of Met on the HGF/SF-Met pathway. EXPERIMENTAL DESIGN: 
      Using our alternative splicing modeling platform LEADS, we have identified a 
      novel splice variant of the Met receptor, which encodes a truncated soluble form 
      of the receptor. This variant was produced as a recombinant Fc-fused protein 
      named Cgen-241A and was tested in various cell-based assays representing 
      different outcomes of the HGF/SF-Met pathway. RESULTS: Cgen-241A significantly 
      inhibited HGF/SF-induced Met phosphorylation as well as cell proliferation and 
      survival. In addition, Cgen-241A showed a profound inhibitory effect on cell 
      scattering, invasion, and urokinase up-regulation. The inhibitory effects of 
      Cgen-241A were shown in multiple human and nonhuman cell types, representing 
      different modes of Met activation. Furthermore, Cgen-241A showed direct binding 
      to HGF/SF. CONCLUSIONS: Taken together, our results indicate that Cgen-241A is a 
      potent antagonist of the HGF/SF-Met pathway, underlining its potential as a 
      therapeutic agent for the treatment of a wide variety of human malignancies that 
      are dependent on this pathway.
FAU - Tiran, Zohar
AU  - Tiran Z
AD  - Compugen Ltd., Tel Aviv, Israel. zohar.tiran@cgen.com
FAU - Oren, Anat
AU  - Oren A
FAU - Hermesh, Chen
AU  - Hermesh C
FAU - Rotman, Galit
AU  - Rotman G
FAU - Levine, Zurit
AU  - Levine Z
FAU - Amitai, Hagit
AU  - Amitai H
FAU - Handelsman, Tal
AU  - Handelsman T
FAU - Beiman, Merav
AU  - Beiman M
FAU - Chen, Aviva
AU  - Chen A
FAU - Landesman-Milo, Dalit
AU  - Landesman-Milo D
FAU - Dassa, Liat
AU  - Dassa L
FAU - Peres, Yair
AU  - Peres Y
FAU - Koifman, Cynthia
AU  - Koifman C
FAU - Glezer, Sarit
AU  - Glezer S
FAU - Vidal-Finkelstein, Rinat
AU  - Vidal-Finkelstein R
FAU - Bahat, Kobi
AU  - Bahat K
FAU - Pergam, Tania
AU  - Pergam T
FAU - Israel, Cylia
AU  - Israel C
FAU - Horev, Judith
AU  - Horev J
FAU - Tsarfaty, Ilan
AU  - Tsarfaty I
FAU - Ayalon-Soffer, Michal
AU  - Ayalon-Soffer M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Protein Isoforms)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis/physiology
MH  - Blotting, Western
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Flow Cytometry
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Protein Isoforms/genetics/metabolism
MH  - Proto-Oncogene Proteins c-met/*genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*physiology
MH  - Surface Plasmon Resonance
EDAT- 2008/07/17 09:00
MHDA- 2008/09/17 09:00
CRDT- 2008/07/17 09:00
PHST- 2008/07/17 09:00 [pubmed]
PHST- 2008/09/17 09:00 [medline]
PHST- 2008/07/17 09:00 [entrez]
AID - 14/14/4612 [pii]
AID - 10.1158/1078-0432.CCR-08-0108 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Jul 15;14(14):4612-21. doi: 10.1158/1078-0432.CCR-08-0108.