PMID- 15102692
OWN - NLM
STAT- MEDLINE
DCOM- 20041210
LR  - 20191108
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 10
IP  - 8
DP  - 2004 Apr 15
TI  - Comprehensive analysis of matrix metalloproteinase and tissue inhibitor 
      expression in pancreatic cancer: increased expression of matrix 
      metalloproteinase-7 predicts poor survival.
PG  - 2832-45
AB  - PURPOSE: To enable the design of improved inhibitors of matrix metalloproteinases 
      (MMPs) for the treatment of pancreatic cancer, the expression profiles of a range 
      of MMPs and tissue inhibitors of MMPs (TIMPs) were determined. EXPERIMENTAL 
      DESIGN: Nine MMPs (MMPs 1-3, 7-9, 11, 12, and 14) and three TIMPs (TIMPs 1-3) 
      were examined in up to 75 pancreatic ductal adenocarcinomas and 10 normal 
      pancreata by immunohistochemistry. Eighteen additional pancreatic ductal 
      adenocarcinomas and an additional eight normal pancreata were also analyzed by 
      real-time reverse transcription-PCR and additionally for MMP-15. RESULTS: There 
      was increased expression by immunohistochemistry for MMPs 7, 8, 9, and 11 and 
      TIMP-3 in pancreatic cancer compared with normal pancreas (P < 0.0001, 0.04, 
      0.0009, 0.005, and 0.0001, respectively). Real-time reverse transcription-PCR 
      showed a significant increase in mRNA levels for MMP-11 in tumor tissue compared 
      with normal pancreatic tissue (P = 0.0005) and also significantly reduced levels 
      of MMP-15 (P = 0.0026). Univariate analysis revealed that survival was reduced by 
      lymph node involvement (P = 0.0007) and increased expression of MMP-7 (P = 0.005) 
      and (for the first time) MMP-11 (P = 0.02) but not reduced by tumor grade, tumor 
      diameter, positive resection margins, adjuvant treatment, or expression of the 
      remaining MMPs and TIMPs. On multivariate analysis, only MMP-7 predicted 
      shortened survival (P < 0.05); however, increased MMP-11 expression was strongly 
      associated with lymph node involvement (P = 0.0073). CONCLUSIONS: We propose that 
      the principle specificity for effective inhibitors of MMPs in pancreatic cancer 
      should be for MMP-7 with secondary specificity against MMP-11. Moreover, these 
      studies indicate that MMP-7 expression is a powerful independent prognostic 
      indicator and potentially of considerable clinical value.
FAU - Jones, Lucie E
AU  - Jones LE
AD  - Department of Surgery, University of Liverpool, Liverpool, United Kingdom.
FAU - Humphreys, Michelle J
AU  - Humphreys MJ
FAU - Campbell, Fiona
AU  - Campbell F
FAU - Neoptolemos, John P
AU  - Neoptolemos JP
FAU - Boyd, Mark T
AU  - Boyd MT
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 (Antibodies, Monoclonal)
RN  - 0 (DNA, Complementary)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 11)
RN  - EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.23 (Matrix Metalloproteinase 7)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/chemistry
MH  - DNA, Complementary/metabolism
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphatic Metastasis
MH  - Male
MH  - Matrix Metalloproteinase 11
MH  - Matrix Metalloproteinase 7/*biosynthesis/*physiology
MH  - Matrix Metalloproteinases, Membrane-Associated
MH  - Metalloendopeptidases/biosynthesis
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Pancreatic Neoplasms/*enzymology/metabolism/*mortality
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Treatment Outcome
EDAT- 2004/04/23 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/04/23 05:00
PHST- 2004/04/23 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/04/23 05:00 [entrez]
AID - 10.1158/1078-0432.ccr-1157-03 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2004 Apr 15;10(8):2832-45. doi: 10.1158/1078-0432.ccr-1157-03.