Chemistry Reference
In-Depth Information
development, the GSL repertoire is known to change, warranting us to present
further details as indicated above in the fi rst paragraph on the survey of GSL
functions.
10.11
GSL s as Developmental or Differentiation Markers
Due to their function in cell recognition and differentiation it is not surprising
that the expression of certain GSLs is developmentally regulated. This is most
strikingly demonstrated by the so- called stage - specifi c embryonic antigens (SSEAs;
also referred to in Chapter 24), whose expression is affected both quantitatively
and qualitatively. For example, SSEA-3 and - 4 (Gal
β
1,3GalNAc
β
1,3Gal
α
1,4Gal
β
1,
4Glc; NeuAc
1,4Glc) are synthesized during
oogenesis, and are present in oocytes, zygotes and blastulas, until they disappear
at the eight- cell stage. SSEA - 1 (Gal
α
2,3Gal
β
1,3GalNAc
β
1,3Gal
α
1,4Gal
β
1,3Fuc]GlcNAc) is expressed on both
glycolipids and glycoproteins, and initially appears at the eight- cell stage. Specifi c
modifi cations of the oligosaccharide chain like acetylation of neuraminic acid resi-
dues of gangliosides or sulfation of neutral GSLs like lactosylceramide are also
involved in embryogenesis, particularly in the development of the nervous system.
In general, changes of expression of GSLs during development and cell differentia-
tion of the nervous system are very well documented [20] (for distinct functions
of GSLs in the nervous system, please see Chapter 30). Lymphocyte differentiation
provides an example of how differential glycosyltransferase activation triggers dif-
ferentiation - dependent expression profi les of GSLs [21] (for further details on
regulation of glycosyltransferases in this system, please see Chapter 27 ). Embry-
onic GSL antigens have been found to reemerge in tumors, thus representing
oncofetal antigens.
β
1,4[
α
10.12
Tumor - Associated GSL Antigens
Aberrant glycosylation is observed in all types of experimental human cancers
and a variety of tumor-associated glycoantigens were identifi ed as carbohydrate
chains of GSLs, in particular among gangliosides (GM2, GD2, GD3, fucosyl-
GM1), Lewis -related GSL and neutral GSLs of the globo series (examples given
in Table 10.5). These GSLs have attracted considerable interest due to the poten-
tial of these antigens as determinants for the diagnosis and targeting of immu-
notherapy. The use of GSLs for antibody production to tumor- associated antigens
shows advantages, because a GSLs can be purifi ed to homogeneity, whereas
glycoproteins often show microheterogeneity in their carbohydrate moieties,
establishing glycoforms. Since GSL antigens can be shed into circulating blood,
their immunological detection could become a marker in early diagnosis. Finally,
several clinical trials indicate that tumor-associated GSL antigens (like GD2 for
