PMID- 12773985
OWN - NLM
STAT- MEDLINE
DCOM- 20030630
LR  - 20091119
IS  - 0039-6060 (Print)
IS  - 0039-6060 (Linking)
VI  - 133
IP  - 5
DP  - 2003 May
TI  - Intestinal transformation results in transforming growth factor-beta-dependent 
      alteration in tumor cell-cell matrix interactions.
PG  - 568-79
AB  - BACKGROUND: An alteration in the expression of and response to transforming 
      growth factor-beta 1 (TGF-beta 1) appears to be an important event during 
      colorectal carcinogenesis. However, the precise role of TGF-beta 1 in colorectal 
      carcinogenesis is not clear. We have previously described in detail the changes 
      in cell proliferation and differentiation caused by chronic exposure to TGF-beta 
      1. In this study we sought to better characterize the changes in tumor cell-cell 
      matrix interactions seen during TGF-beta 1-mediated intestinal transformation. 
      METHODS: Rat intestinal epithelial cells (RIE) and RIE cells transformed by 
      chronic exposure to TGF-beta 1 (RIE-Tr) were treated with TGF-beta 1 and 
      production of components of the plasmin/plasminogen system measured by ELISA and 
      Western blotting. TGF-beta 1 effects on invasion and adhesion were determined in 
      vitro. The role of urokinase on TGF-beta 1-mediated invasion and adhesion were 
      determined using immunoneutralization. The role of COX-2 was determined using a 
      specific COS-2 inhibitor. RESULTS: TGF-beta 1 had no effect on RIE-1 adhesion to 
      collagen types I and IV, fibronectin, and laminin, or invasion through collagen 
      types I and IV. However, 5 ng/mL TGF-beta 1 significantly increased the 
      invasiveness and decreased the adhesiveness of RIE-Tr. This effect of TGF-beta 1 
      on RIE-Tr was associated with a significant increase in plasmin activity 
      secondary to increased expression of uPA. TGF-beta 1 had no effect on either uPA 
      receptor or PAI-1 in this system. Antibodies to uPA completely blocked the 
      TGF-beta 1-mediated invasiveness of the RIE-Tr cells and returned their 
      adhesiveness to basement membrane proteins to baseline. Addition of the selective 
      Cox-2 inhibitor SC-58125 resulted in a dose-dependent decrease in TGF-beta 
      1-mediated invasion and uPA expression. CONCLUSION: This study provides 
      additional evidence for TGF-beta 1 as a tumor promoter during intestinal 
      carcinogenesis and a possible new mechanism for Cox-2-related colon 
      carcinogenesis.
FAU - Berger, David H
AU  - Berger DH
AD  - Department of Surgery, Baylor College of Medicine, and the Veterans Affairs 
      Medical Center, Houston, TX 77030, USA.
FAU - O'Mahony, Christine A
AU  - O'Mahony CA
FAU - Sheng, Hongmiao
AU  - Sheng H
FAU - Shao, Jinyi
AU  - Shao J
FAU - Albo, Daniel
AU  - Albo D
FAU - DuBois, Raymond N
AU  - DuBois RN
FAU - Beauchamp, R Daniel
AU  - Beauchamp RD
LA  - eng
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - CA69457/CA/NCI NIH HHS/United States
GR  - DK-52334/DK/NIDDK NIH HHS/United States
GR  - DK47297/DK/NIDDK NIH HHS/United States
GR  - ES00267/ES/NIEHS NIH HHS/United States
GR  - P01-CA 77839/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Surgery
JT  - Surgery
JID - 0417347
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 0 (Pyrazoles)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 162054-19-5 
      (1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Cell Adhesion/drug effects
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Cell Transformation, Neoplastic/*chemically induced
MH  - Cells, Cultured
MH  - Cyclooxygenase 2
MH  - Cyclooxygenase 2 Inhibitors
MH  - Cyclooxygenase Inhibitors/administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Extracellular Matrix/*physiology
MH  - Fibrinolysin/metabolism
MH  - Intestinal Mucosa/*physiopathology
MH  - Isoenzymes/antagonists & inhibitors
MH  - Neoplasm Invasiveness
MH  - Prostaglandin-Endoperoxide Synthases
MH  - Pyrazoles/administration & dosage
MH  - Rats
MH  - Transforming Growth Factor beta/metabolism/*pharmacology
MH  - Transforming Growth Factor beta1
MH  - Urokinase-Type Plasminogen Activator/metabolism
EDAT- 2003/05/30 05:00
MHDA- 2003/07/02 05:00
CRDT- 2003/05/30 05:00
PHST- 2003/05/30 05:00 [pubmed]
PHST- 2003/07/02 05:00 [medline]
PHST- 2003/05/30 05:00 [entrez]
AID - S0039606003000291 [pii]
AID - 10.1067/msy.2003.125 [doi]
PST - ppublish
SO  - Surgery. 2003 May;133(5):568-79. doi: 10.1067/msy.2003.125.