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Polymorphic expression of decay-accelerating factor in human colorectal cancer.
M Nakagawa1, M Mizuno, M Kawada
1First Department of Internal Medicine, Okayama University Medical School, Japan.
Journal of Gastroenterology and Hepatology
|February 24, 2001
Summary
Colorectal cancer (CRC) shows increased decay-accelerating factor (DAF) expression. Variability in DAF
Area of Science:
- Biochemistry
- Oncology
- Immunology
Background:
- Decay-accelerating factor (DAF), a complement regulatory protein, is upregulated in colorectal cancer (CRC) glands and detectable in patient stool.
- DAF's presence in stool may depend on its cell surface stability, influenced by protein glycosylation.
- Previous studies indicated enhanced DAF expression in CRC, prompting further biochemical investigation.
Purpose of the Study:
- To biochemically analyze DAF expression in colorectal cancer.
- To elucidate the mechanism of DAF release from human colorectal cancers.
- To investigate the role of glycosylation in DAF shedding.
Main Methods:
- Western and northern blotting were used to analyze DAF expression in 10 surgically resected colorectal cancer specimens.
- Glycosidase digestion was employed to analyze the glycosylation patterns of DAF protein.
Main Results:
- Northern blot analysis revealed a two- to threefold increase in DAF mRNA expression in colorectal cancer tissues compared to normal tissues.
- Western blotting showed elevated DAF protein levels in cancer tissues, with observed heterogeneity in apparent molecular weight among patients.
- Removal of O-linked sugars reduced the observed heterogeneity in DAF size.
Conclusions:
- The polymorphic expression of DAF in colorectal cancer is likely attributed to variations in O-glycosylation.
- Altered O-glycosylation may impact DAF's stability on cancer cell surfaces.
- This variability in stability could influence the amount of DAF shed into the stools of colorectal cancer patients.