PMID- 10845563
OWN - NLM
STAT- MEDLINE
DCOM- 20000627
LR  - 20191025
IS  - 0262-0898 (Print)
IS  - 0262-0898 (Linking)
VI  - 17
IP  - 7
DP  - 1999
TI  - Differential modulation of proliferation, matrix metalloproteinase expression and 
      invasion of human head and neck squamous carcinoma cells by c-erbB ligands.
PG  - 631-9
AB  - Evidence suggests that there is an association between the abnormal expression of 
      members of the c-erbB receptor tyrosine kinase family and poor prognosis in head 
      and neck squamous cell carcinomas (HNSCC). Until now, the relative contributions 
      of different c-erbB ligands to HNSCC progression have not been clearly defined. 
      In this paper we examined the effects of ligands with different c-erbB receptor 
      specificities in terms of their stimulation of HNSCC proliferation, expression of 
      matrix metalloproteinases (MMPs) and invasion. Heregulin-beta1 (HRG-beta1; 
      selective c-erbB3/B4 ligand) was found to stimulate proliferation in the majority 
      of cell lines, whereas epidermal growth factor (EGF; EGFR ligand) and 
      betacellulin (BTC; EGFR/B4 ligand) induced variable responses. All three ligands 
      up-regulated multiple MMPs including collagenases, stromelysins, matrilysin and 
      gelatinase B (MMP-9) but had minimal or no effects on gelatinase A (MMP-2), 
      MT1-MMP and tissue inhibitors of MMPs (TIMPs). MMP-9 mRNA was induced to a higher 
      level than other MMPs, although with slower kinetics. HRG-beta1 was less active 
      than EGF and BTC at the optimal concentration (relative potency of EGF:BTC:HRG = 
      3:4:1). In vitro invasion through Matrigel was also increased by all three 
      ligands in proportion to their MMP up-regulation. A specific anti-EGFR monoclonal 
      antibody (mAb ICR62) inhibited MMP up-regulation, migration and invasion induced 
      by all three ligands, whereas an anti-c-erbB-2 mAb ICR12 inhibited mitogenic and 
      motogenic responses following ligand stimulation but had no effect on MMP 
      expression. These results suggest that c-erbB ligands may differentially 
      potentiate the invasive phenotype of HNSCC via co-operative induction of cell 
      proliferation, migration and proteolysis. The EGFR signalling pathway appears to 
      be the dominant component controlling the proteolytic and invasive phenotype in 
      HNSCC, whereas the c-erbB-2 signalling pathway is responsible, in part, for the 
      mitogenic and motogenic effects of ligands.
FAU - O-charoenrat, P
AU  - O-charoenrat P
AD  - Department of Head and Neck Surgery, Royal Marsden Hospital, London, UK. 
      pornchai@icr.ac.uk
FAU - Rhys-Evans, P
AU  - Rhys-Evans P
FAU - Court, W J
AU  - Court WJ
FAU - Box, G M
AU  - Box GM
FAU - Eccles, S A
AU  - Eccles SA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Clin Exp Metastasis
JT  - Clinical & experimental metastasis
JID - 8409970
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (BTC protein, human)
RN  - 0 (Betacellulin)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Growth Substances)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Ligands)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Neuregulin-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 155646-83-6 (heregulin beta1)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology
MH  - Betacellulin
MH  - Carcinoma, Squamous Cell/enzymology/*pathology
MH  - Cell Division/drug effects
MH  - Culture Media, Conditioned
MH  - Enzyme Induction/drug effects
MH  - Epidermal Growth Factor/*pharmacology
MH  - ErbB Receptors/immunology
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Growth Substances/*pharmacology
MH  - Head and Neck Neoplasms/enzymology/*pathology
MH  - Humans
MH  - *Intercellular Signaling Peptides and Proteins
MH  - Ligands
MH  - Metalloendopeptidases/*biosynthesis/genetics
MH  - Neoplasm Invasiveness/*physiopathology/prevention & control
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Neuregulin-1/*pharmacology
MH  - Pharyngeal Neoplasms/enzymology/genetics/pathology
MH  - Phenotype
MH  - Receptor, ErbB-2/immunology/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Tissue Inhibitor of Metalloproteinase-1/biosynthesis/genetics
MH  - Tissue Inhibitor of Metalloproteinase-2/biosynthesis/genetics
MH  - Tumor Cells, Cultured
EDAT- 2000/06/14 09:00
MHDA- 2000/07/06 11:00
CRDT- 2000/06/14 09:00
PHST- 2000/06/14 09:00 [pubmed]
PHST- 2000/07/06 11:00 [medline]
PHST- 2000/06/14 09:00 [entrez]
AID - 10.1023/a:1006751016860 [doi]
PST - ppublish
SO  - Clin Exp Metastasis. 1999;17(7):631-9. doi: 10.1023/a:1006751016860.