PMID- 10699931
OWN - NLM
STAT- MEDLINE
DCOM- 20000322
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 85
IP  - 4
DP  - 2000 Feb 15
TI  - Nk4, a new HGF/SF variant, is an antagonist to the influence of HGF/SF on the 
      motility and invasion of colon cancer cells.
PG  - 563-70
AB  - Hepatocyte Growth Factor/Scatter Factor (HGF/SF) is a heterodimeric molecule that 
      plays a key role in the regulation of migration, invasion and angiogenesis in 
      cancer, via activation of its receptor, c-met. HGF/SF is composed of an 
      alpha-chain, containing the N-terminal hairpin domain and 4 kringle domains, plus 
      the serine protease-like beta-chain. We have examined here the properties of NK4, 
      an HGF variant containing the N-terminal hairpin plus the 4 kringle domains, on 
      tumour cell proliferation, dissociation and invasion using human colorectal 
      cancer cells (HT115). The expression of HGF/SF and its receptor was also examined 
      by RT-PCR and Western blotting. Analysis revealed NK4 to be an HGF/SF antagonist 
      that, at a wide range of concentrations, did not exert any biological effects of 
      its own. HT115 cells were shown to express the HGF/SF receptor mRNA and protein. 
      HGF/SF-induced receptor tyrosine phosphorylation was suppressed, in a 
      dose-dependent manner, upon addition of NK4, whereas the addition of NK4 alone 
      caused no phosphorylation. Tumour cell motility was induced by HGF and inhibited 
      by NK4. Furthermore, HGF/SF induced the invasion of cells through Matrigel 
      basement membrane components, and again this induced invasion was suppressed by 
      NK4. Our results show that the ability of HGF/SF to stimulate tumour cell 
      motility and invasion, properties required for metastatic spread, can be 
      inhibited by NK4. Thus, NK4 may have an important role in the control of cancer 
      metastasis.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Parr, C
AU  - Parr C
AD  - University Department of Surgery, University of Wales College of Medicine, 
      Cardiff, UK. Parrc@cf.ac.uk
FAU - Hiscox, S
AU  - Hiscox S
FAU - Nakamura, T
AU  - Nakamura T
FAU - Matsumoto, K
AU  - Matsumoto K
FAU - Jiang, W G
AU  - Jiang WG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Recombinant Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Movement/*drug effects
MH  - Colonic Neoplasms/*pathology/*physiopathology
MH  - Colorectal Neoplasms/pathology/physiopathology
MH  - Dogs
MH  - Hepatocyte Growth Factor/*genetics/pharmacology/*physiology
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-met/genetics/metabolism/*physiology
MH  - Recombinant Proteins/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Cells, Cultured
EDAT- 2000/03/04 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/03/04 09:00
PHST- 2000/03/04 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/03/04 09:00 [entrez]
AID - 10.1002/(SICI)1097-0215(20000215)85:4<563::AID-IJC19>3.0.CO;2-D [pii]
PST - ppublish
SO  - Int J Cancer. 2000 Feb 15;85(4):563-70.