PMID- 12807719
OWN - NLM
STAT- MEDLINE
DCOM- 20030916
LR  - 20220409
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 24
IP  - 8
DP  - 2003 Aug
TI  - Growth and angiogenesis of human breast cancer in a nude mouse tumour model is 
      reduced by NK4, a HGF/SF antagonist.
PG  - 1317-23
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a cytokine primarily produced 
      by stromal fibroblasts and is a known angiogenic and invasion-inducing factor. It 
      is increased in patients with breast cancer. This study examined the effect of 
      NK4, a newly described HGF/SF antagonist, on HGF/SF-promoted growth of a human 
      breast cancer. Both in vitro (invasion and migration assays) and in vivo (murine 
      tumour model) methods were used to ascertain the effect of NK4 on HGF/SF from two 
      sources: human fibroblast-derived HGF/SF and recombinant HGF/SF. In the in vitro 
      invasion assay and migration assay, both HGF/SF and human fibroblasts, which 
      secrete bioactive HGF/SF, increased the invasiveness and migration of the breast 
      cancer cells (MDA MB 231). NK4 significantly reduced this invasiveness and 
      motility. In the animal model, tumour volume and weight was significantly reduced 
      with addition of NK4. It also suppressed HGF/SF-induced growth and markedly 
      retarded tumour growth induced by fibroblasts (MRC5), secreting bioactive HGF/SF. 
      Tumour angiogenesis was assessed by immunohistochemical staining of primary 
      tissue sections using VE-cadherin (an endothelial cell specific cell-cell 
      adhesion molecule). Again, NK4 reduced the effects of both HGF/SF and 
      fibroblasts. We conclude that NK4 has a significant effect on the growth of human 
      breast tumours in nude mice, particularly when stimulated by HGF/SF or 
      fibroblasts. This may occur by decreasing angiogenesis. This gives a clear 
      indication of the therapeutic worth of NK4.
FAU - Martin, Tracey A
AU  - Martin TA
AD  - Metastasis Research Group, University Department of Surgery, University of Wales 
      College of Medicine, Heath Park, Cardiff CF14 4XN, UK. martinya1@cf.ac.uk
FAU - Parr, Christian
AU  - Parr C
FAU - Davies, Gaynor
AU  - Davies G
FAU - Watkins, Gareth
AU  - Watkins G
FAU - Lane, Jane
AU  - Lane J
FAU - Matsumoto, Kunio
AU  - Matsumoto K
FAU - Nakamura, T
AU  - Nakamura T
FAU - Mansel, Robert E
AU  - Mansel RE
FAU - Jiang, Wen G
AU  - Jiang WG
LA  - eng
GR  - 1999:73/BCN_/Breast Cancer Now/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030509
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (HGF protein, human)
RN  - 0 (Mitogens)
RN  - 0 (PXN protein, human)
RN  - 0 (Paxillin)
RN  - 0 (Phosphoproteins)
RN  - 0 (Pxn protein, mouse)
RN  - 42HK56048U (Tyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Breast Neoplasms/*blood supply/pathology/prevention & control
MH  - Cell Adhesion/drug effects
MH  - Cell Division/drug effects
MH  - Cell Movement/*drug effects
MH  - Cytoskeletal Proteins/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Fibroblasts/drug effects
MH  - Gene Expression Regulation, Neoplastic
MH  - Hepatocyte Growth Factor/genetics/metabolism/*pharmacology
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - *Mitogens
MH  - Neoplasm Invasiveness/pathology/*prevention & control
MH  - Neovascularization, Pathologic/metabolism/pathology/*prevention & control
MH  - Paxillin
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-met/metabolism
MH  - Survival Rate
MH  - Tumor Cells, Cultured
MH  - Tyrosine/metabolism
EDAT- 2003/06/17 05:00
MHDA- 2003/09/17 05:00
CRDT- 2003/06/17 05:00
PHST- 2003/06/17 05:00 [pubmed]
PHST- 2003/09/17 05:00 [medline]
PHST- 2003/06/17 05:00 [entrez]
AID - bgg072 [pii]
AID - 10.1093/carcin/bgg072 [doi]
PST - ppublish
SO  - Carcinogenesis. 2003 Aug;24(8):1317-23. doi: 10.1093/carcin/bgg072. Epub 2003 May 
      9.