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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1067/msy.2003.125 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.
Protein Sci
February 2025
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA.
The TGF-β family ligand Nodal is an essential regulator of embryonic development, orchestrating key processes such as germ layer specification and body axis formation through activation of SMAD2/3-mediated signaling. Significantly, this activation requires the co-receptor Cripto-1. However, despite their essential roles in embryogenesis, the molecular mechanism through which Cripto-1 enables Nodal to activate the SMAD2/3 pathway has remained elusive.
View Article and Find Full Text PDFSilencing Map3k7 suppresses pyroptosis to alleviate bronchopulmonary dysplasia through inhibiting the TGF-β1/Smad3 pathway.
Gen Physiol Biophys
January 2025
Department of Pediatrics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China.
Bronchopulmonary dysplasia (BPD) is a serious complication in premature infants. This study aimed to investigate the mechanism of mitogen-activated protein 3 kinase 7 (Map3k7) affecting BPD by regulating caspase-1 mediated pyroptosis. The morphology of the lung tissue was observed using hematoxylin-eosin staining.
View Article and Find Full Text PDFMechanistic insights into Y-Box binding protein-1 mediated regulation of lipid metabolism and oxidative stress in NAFLD via INHBE/TNF-β pathway.
Biomol Biomed
December 2024
The Gastroenterology Department, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
Article Synopsis
- Nonalcoholic fatty liver disease (NAFLD) has become a significant public health issue, prompting this study to explore the effects of Y-box binding protein-1 (YB1) knockdown on lipid metabolism and oxidative stress in liver cells influenced by palmitic acid.
- The research found that knocking down YB1 leads to significant changes in gene expression, with 798 differentially expressed genes identified, and it enhances cell viability while improving lipid metabolism and reducing harmful reactive oxygen species.
- The underlying mechanism primarily involves the INHBE/TNF-β signaling pathway, indicating that targeting YB1 may present new therapeutic options for managing NAFLD.
ARP2/3 complex affects myofibroblast differentiation and migration in pancreatic ductal adenocarcinoma.
Int J Cancer
March 2025
Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Article Synopsis
- The ARP2/3 complex plays a crucial role in the organization of the actin cytoskeleton and the formation of structures called lamellipodia, which are important in the progression of pancreatic ductal adenocarcinoma (PDAC).
- This study investigates how the ARP2/3 complex affects cancer-associated fibroblasts (CAFs) that contribute to PDAC advancement and patient survival, using mouse models and human cell studies.
- Results indicate that the ARP2/3 complex is vital for CAF migration and differentiation, suggesting that targeting it could be an effective new approach for treating PDAC.
Spatiotemporal EP4-fibulin-1 expression is associated with vascular intimal hyperplasia.
Cardiovasc Res
December 2024
Department of Physiology, Tokyo Medical University, Tokyo, Japan.
Article Synopsis
- The study aims to understand the role of the PGE2 receptor EP4 in vascular intimal hyperplasia (IH), noting its differing effects in vascular smooth muscle cells (VSMCs) and endothelial cells.
- Researchers generated EP4 reporter mice and found that EP4 expression peaks in VSMCs two weeks post-femoral artery injury, affecting IH's progression based on EP4 levels in these cells.
- The downstream effects of EP4 signaling in VSMCs were explored, revealing that EP4 promotes VSMC proliferation and migration through fibulin-1 and its interaction with ECM1, suggesting that targeting this signaling pathway could be a potential therapeutic approach to manage IH.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!