Chemistry Reference
In-Depth Information
27.9
Glycosylation in Infl ammatory Bowel Diseases
As an example for chronic infl ammatory diseases we here deal in more detail with
colitis ulcerosa and Crohn's disease both known under the term infl ammatory
bowel diseases (IBD), which - being chronic infl ammatory processes - have a high
risk of turning into colorectal cancer [16]. Although the etiology of these two dis-
eases is not quite clear, there are many indications that point to an autoimmune
mechanism, possibly induced by an immune response of the host to the intestinal
microfl ora. With regard to mucosal glycosylation, it is striking that similar changes
can be observed in IBD as in carcinoma. One predominant change is the blockade
of chain elongation to core 2
O
-glycosylation by a quantitative change in the res-
pective glycosyltransferases, and a concomitant increase in smaller carbohydrate
sequences such as the TF structure (CD176) or the even shorter Tn/sialylated Tn
glycan (CD175/CD175s) (Figure 27.4). CD176 is indeed a marker for malignancy,
e.g., colon cancer, and its expression increases with malignancy. The unmasked
CD176 surface structure is rarely found on normal cells. However, in its sialylated
form, CD176 is expressed on almost all hematopoietic cells and many other
somatic cells. One reason for the lack of CD176 expression on normal cells is that
it may represent a signal for negative selection and can, upon linkage with respec-
Figure 27.4
Synthesis pathway of
O
- glycans of
mucin-type glycoproteins. Under certain cir-
cumstances, e.g., tumorigenesis, the synthesis
towards core 2 glycans stops due to down-
regulation of the respective
β
1,6 - N - acetyl -
glucosaminyl - transferase (C2GnT), with the
consequence that glycoproteins carry shorter
core 1 glycans like CD175 (Tn) or CD176 (TF).
Expression of terminal CD176 structures under
normal conditions is a rare event, possibly
because it may transfer apoptosis signals. For
tumor cells this may be advantageous, because
CD176 may help metastasizing tumor cells to
adhere to the asialoglycoprotein receptor of
liver tissue.
