Glycans as Functional Markers in Malignancy? - The Sugar Code - page 429

please see Table 18.1) (Figure 25.2). As galectin-1 expression is at the same
time upregulated, similarly noted in the studies on neuroblastoma, the status
of sialylation acts as molecular switch-on signal for galectin-1 binding also in
this case [12]. In detail, the tumor suppressor works via transcriptional
upregulation of lectin/enzymes of the glycosylation machinery, and - at the
same time - the cell surface presence of a likely effector target glycoprotein of
galectin - 1 (the fi bronectin receptor) is elevated, thereby completing an
orchestrated interplay between glycan remodeling and lectin expression [13].
How such a functional interplay is clinically manifested during tumor
progression is presented in the third example.

c) Cutaneous T cell lymphoma cells in the Sézary syndrome are known to lose
distinct surface markers in the course of disease progression, especially the
CD7 antigen. Its absence renders these tumor cells resistant to the induction
of apoptosis with galectin-1 as effector [14]. In contrast, CD7 + cells undergo
lectin-induced apoptosis so that the differential sensitivity to the tissue lectin
may well be tied to the shift in subpopulations of this tumor type [14] .

These three examples highlight the exquisite target specifi city of an endogenous
lectin for functional cell surface ligands (for further examples of orchestration of
lectin - glycan expression in infl ammation, please see Chapter 27 ). Despite sharing
monosaccharide specifi city, plant and human lectins cannot be expected to have
identical fi ne - specifi city profi les due to their structural disparities. Practically, the
experimental data shown in Figure 25.2 illustrate that the binding characteristics
of cell populations for an endogenous lectin can entail functional implications,
in this case ascertained by measuring galectin- 1 - induced anoikis [13] . Thus, appli-
cation of endogenous lectins as tool (Table 25.1) can be a salient step to track
down lectin-triggered effector mechanisms. They will comprise a series of intra-
cellular signaling steps leading from the initial binding step to the cellular
response. An example for the intracellular signaling pathway following cell
surface binding is shown in Figure 25.3 for the galectin-1-dependent cell cycle

regulated protein kinases 1 and 2 (ERK1/2) by
sequential transphosphorylation. Active (phos-
phorylated) form of proteins is marked by a
small-encircled P. The phosphorylated ERK1/2
translocates from the cytosol to the nucleus
and here phosphorylates the transcription
factor signaling protein 1 (Sp1). As a conse-
quence, the binding of this protein to the pro-
moter of the p27 KIP1 gene (p27 prom) is
abrogated. The protein p27 KIP1 is a cyclin-depen-
dent kinase (CDK) inhibitor. It acts on cyclin
E/A - cyclin - dependent kinase 2 (CDK2) com-
plexes blocking cell cycle progression. As a
result of the downregulation of its expression,
cells can now enter the S phase. (Bottom panel,
right column) In contrast, the interaction of the

galectin-1 homodimer with the integrin does
not trigger engagement of Ras, which remains
in its inactive (GDP-loaded) form. This pre-
vents the activation of the MAPK pathway, its
components remain inactive (unphosphory-
lated). Without being phosphorylated, Sp1
induces transcription of the p27 KIP1 gene after
binding to its promoter (p27 prom). The pro-
duced p27 KIP1 protein (p27) then associates
with cyclin E/A-CDK2 complexes, causing G 1
arrest. The abbreviations ' ext ' , ' cyt ' and ' ncl ' ,
respectively, denote the extracellular, cytosolic
and nuclear compartments. The two crosses
signify that the respective process is blocked
(for experimental details, please see [15]).