Altered Expression of Caspases-4 and -5 during Inflammatory Bowel Disease and Colorectal Cancer - Novel Diagnostic and Therapeutic Potential.
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Journal ArticleDate:
2015Access:
openAccessCitation:
Flood, B., Oficjalska, K., Laukens, D., Fay, J., Mills, K.H., Sheahan, K., Ryan, E.J., Doherty, G.A., Kay, E.W. and Creagh, E.M., Altered Expression of Caspases-4 and -5 during Inflammatory Bowel Disease and Colorectal Cancer - Novel Diagnostic and Therapeutic Potential., Clinical and Experimental Immunology, 181, 1, 2015, 39-50Download Item:
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Abstract:
Caspases are a group of proteolytic enzymes involved in the co-ordination
of cellular processes, including cellular homeostasis, inflammation and
apoptosis. Altered activity of caspases, particularly caspase-1, has been
implicated in the development of intestinal diseases, such as inflammatory
bowel disease (IBD) and colorectal cancer (CRC). However, the
involvement of two related inflammatory caspase members, caspases-4
and -5, during intestinal homeostasis and disease has not yet been
established. This study demonstrates that caspases-4 and -5 are involved
in IBD-associated intestinal inflammation. Furthermore, we found a clear
correlation between stromal caspase-4 and -5 expression levels,
inflammation and disease activity in ulcerative colitis patients.
Deregulated intestinal inflammation in IBD patients is associated with an
increased risk of developing CRC. We found robust expression of
caspases-4 and -5 within intestinal epithelial cells, exclusively within
neoplastic tissue, of colorectal tumours. An examination of adjacent
normal, inflamed and tumour tissue from patients with colitis-associated
CRC confirmed that stromal expression of caspases-4 and -5 is increased
in inflamed and dysplastic tissue, while epithelial expression is restricted
to neoplastic tissue. In addition to identifying caspases-4 and -5 as
potential targets for limiting intestinal inflammation, this study has
identified epithelial-expressed caspases-4 and -5 as biomarkers with
diagnostic and therapeutic potential in CRC.
Sponsor
Grant Number
Higher Education Authority (HEA)
scheme #201921, award # 12259
Wellcome Trust
WT#078306
Science Foundation Ireland (SFI)
SFI, 12/IP/1400
Author's Homepage:
http://people.tcd.ie/ecreaghhttp://people.tcd.ie/millsk
Description:
PUBLISHED
Author: MILLS, KINGSTON; CREAGH, EMMA
Type of material:
Journal ArticleCollections:
Series/Report no:
Clinical and Experimental Immunology181
1
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Full text availableSubject (TCD):
Cancer , Immunology, Inflammation & Infection , COLORECTAL CANCER , Cancer Detection , INFLAMMATORY BOWEL DISEASE , InflammationDOI:
http://dx.doi.org/10.1111/cei.12617Licences: