PMID- 17625304
OWN - NLM
STAT- MEDLINE
DCOM- 20070920
LR  - 20131121
IS  - 1590-8577 (Electronic)
IS  - 1590-8577 (Linking)
VI  - 8
IP  - 4 Suppl
DP  - 2007 Jul 9
TI  - Action of antiproteases on pancreatic cancer cells.
PG  - 479-87
AB  - Tumor-associated trypsinogen, urokinase-type plasminogen activator, matrix 
      metalloprotease-2 (MMP-2), and MMP-9 each play a dominant role in the degradation 
      of the extracellular matrix (ECM) during the invasion process of pancreatic 
      cancer. Transforming growth factor beta1 (TGF-beta1) is a multifunctional 
      polypeptide that regulates cell growth and differentiation, extracellular matrix 
      deposition, cellular adhesion properties, angiogenesis and also immune functions. 
      The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor which 
      is cleaved and activated by trypsin and tryptase. PAR-2 activated by trypsin 
      plays an important role in promoting the proliferation of pancreatic cancer. We 
      previously reported that TGF-beta1 up-regulated vascular endothelial growth 
      factor (VEGF) production, and the protease production of both MMP-2 and 
      urokinase-type plasminogen activator in the highly metastatic pancreatic cancer 
      cell lines SW1990 and CAPAN-2. We had examined the inhibitor effects of a 
      protease inhibitor, gabexate mesilate, on cell invasion, cell proliferation, 
      growth factor production, and ECM degradation. We also examined the effect of 
      gabexate mesilate on the production of growth factor and ECM degradation by these 
      cell proteases and enzymatic activities. Gabexate mesilate down-regulated the 
      invasiveness, the proliferation and liver metastasis potential of SW1990 and 
      CAPAN-2 cells. Gabexate mesilate inhibited not only the enzymatic activities of 
      tumor-associated trypsinogen and urokinase-type plasminogen activator but also 
      the production of MMP-2, all of which have been known to be secondarily 
      up-regulated by TGF-beta1. These findings suggested that gabexate mesilate is 
      potentially useful in the treatment against invasion, proliferation, and 
      metastasis of pancreatic cancer.
FAU - Uchima, Yasutake
AU  - Uchima Y
AD  - Department of Surgical Oncology, Osaka City University Graduate School of 
      Medicine, Asahi-machi, Abeno-ku, Osaka, Japan. yasu_uchima@yahoo.co.jp
FAU - Sawada, Tetsuji
AU  - Sawada T
FAU - Hirakawa, Kosei
AU  - Hirakawa K
LA  - eng
PT  - Journal Article
DEP - 20070709
PL  - England
TA  - JOP
JT  - JOP : Journal of the pancreas
JID - 101091810
RN  - 0 (Protease Inhibitors)
RN  - 0 (Receptor, PAR-2)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 4V7M9137X9 (Gabexate)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Adenocarcinoma/drug therapy/*enzymology/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Extracellular Matrix/*enzymology
MH  - Gabexate/therapeutic use
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Pancreatic Neoplasms/drug therapy/*enzymology/pathology
MH  - Peptide Hydrolases/*metabolism
MH  - Protease Inhibitors/*metabolism/therapeutic use
MH  - Receptor, PAR-2/metabolism
MH  - Transforming Growth Factor beta1/metabolism
EDAT- 2007/08/02 09:00
MHDA- 2007/09/21 09:00
CRDT- 2007/08/02 09:00
PHST- 2007/08/02 09:00 [pubmed]
PHST- 2007/09/21 09:00 [medline]
PHST- 2007/08/02 09:00 [entrez]
AID - v08i04a17 [pii]
PST - epublish
SO  - JOP. 2007 Jul 9;8(4 Suppl):479-87.