Chemistry Reference
In-Depth Information
Figure 21.3
Model of intercellular recognition
mediated by GSLs (adapted from [9]). The
early event in cell recognition consists of high-
ly specifi c, low-affi nity and polyvalent interac-
tions between the carbohydrate moieties of
GSLs at the cell surface (left panel). The poly-
valency is obtained through organization of
GSLs into microdomains (see Chapter 10). This
initial step is subsequently reinforced by pro-
tein - carbohydrate interactions between lectins
and their carbohydrate receptors (see Chapters
13 - 19 ), and protein - protein interactions be-
tween different adhesion molecules (right pan-
el). The binding is associated with signal
transduction. AM, adhesion molecule; CR, car-
bohydrate receptor; GSLs, glycosphingolipids;
L, lectin; TD, signal transducer.
including human) embryo. Homotypic aggregation of 2102 cells is based on inter-
actions between Gb4 and nLc
4
(see Chapter 10 for structures), or between Gb4
and GalGb4 (the major SSEA-3 epitope) [9, 10]. This Gb4-dependent adhesion is
thought to be characteristic of the human/primate compaction process that leads
to activation of the transcription factors cAMP-responsive element binding protein
and activation protein 1. In this adhesion system, the possibility of protein- carbo-
hydrate interaction through Gb4- or GalGb4-binding proteins remains to be
studied.
21.2.2.3
GM 3 - Dependent Adhesion
Tumor cell adhesion to endothelial cell s ( EC s) through carbohydrate - carbohydrate
interaction promotes tumor cell metastasis (reviewed in [9, 10], see Chapters 10.8,
25.2 and 30.5 for functional aspects of gangliosides). Metastatic and invasive abili-
ties of mouse melanoma B16 cells are closely correlated with the level of sialosyl-
lactosylceramide (GM3, see Table 10.3 and Figure 30.3 for structures) surface
expression, and also with their degree of adhesion to cultured ECs. Such adhesion
is not selectin- or integrin/intercellular adhesion molecule-dependent, but the
process is based on the heterotypic interaction of GM3 with lactosylceramide and
Gb4 expressed on ECs, where both adhesion and motility are strongly enhanced.
This mechanism is synergistic with integrin-dependent adhesion and motility
(Figure 21.3 ).
