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Alpha2beta1 integrin signalling enhances cyclooxygenase-2 expression in intestinal epithelial cells
Oliver Jay Broom1, Ramin Massoumi, Anita Sjölander
1Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, SE-205 02 Malmö, Sweden.
Journal of Cellular Physiology
|September 15, 2006
Summary
Integrin signaling, activated by extracellular matrix changes in inflammatory bowel diseases (IBD), upregulates cyclooxygenase-2 (COX-2) in intestinal cells, potentially promoting colon cancer development.
Area of Science:
- Cell biology
- Molecular biology
- Gastroenterology
Background:
- Inflammatory bowel diseases (IBD) increase colon cancer risk via inflammation and extracellular matrix (ECM) alterations.
- Inflammation induces cyclooxygenase-2 (COX-2), a key enzyme in colon cancer, through inflammatory mediators.
Purpose of the Study:
- Investigate how integrin signaling affects cyclooxygenase-2 (COX-2) expression in intestinal epithelial cells.
- Determine the role of ECM changes in inflammation-associated colon cancer.
Main Methods:
- Utilized non-transformed intestinal epithelial cell lines (Int 407, IEC-6).
- Assessed integrin expression and activity upon cell adhesion to collagen I/IV.
- Measured COX-2 promoter activity, protein expression, and downstream signaling pathways (PKCalpha, Ras, NFkappaB, Erk1/2, Src).
- Quantified reactive oxygen species (ROS) generation and cell migration.
Main Results:
- Cell adhesion to collagen increased alpha2beta1 integrin expression and activation.
- Integrin activation led to increased COX-2 promoter activity and expression.
- The signaling pathway involved PKCalpha, Ras, and NFkappaB, but not Erk1/2 or Src.
- Increased COX-2 activity resulted in elevated ROS generation and enhanced cell migration.
Conclusions:
- Integrin signaling, triggered by ECM changes, upregulates COX-2 in intestinal epithelial cells.
- This pathway links inflammation-induced ECM modulation to colon cancer promotion via ROS and cell migration.
- Identified a novel mechanism connecting IBD, ECM, integrins, and colon cancer progression.
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