Biomedical Engineering Reference
In-Depth Information
5.2 Selected examples of cell adhesion and motility regulated by galectins-1, -3 and -8
We here present only few examples of galectin function in cell adhesion and motility
processes. The list is by far not complete. Other review articles focus more detailed on cell
adhesion events mediated by galectins (Elola et al., 2007; Hughes, 2001).
Galectin-1 is an important factor for the adhesion and proliferation of neural stem cells and
neural progenitor cells. The adhesion is mediated by the carbohydrate recognition domain
and interaction of this binding domain with integrin β1 subunit (Sakaguchi et al., 2006;
Sakaguchi et al., 2010). Moreover galectin-1 can reduce the motility of immune cells which
might explain parts of its anti-inflammatory effects (Elola et al., 2007; Liu, 2005; Rabinovich
et al., 2002a; Rabinovich et al., 2002b).
One important function of galectin-3 is associated with angiogenesis (Nangia-Makker et al.,
2000a; Nangia-Makker et al., 2000b). Galectin-3 increases for example angiogenesis by
forming integrin αvβ3 lattices on the cell-surface leading to FAK regulated downstream
signalling. Galectin-3 mediated angiogenesis depends on the growth factors VEGF and
bFGF (Markowska et al., 2010). Another interesting function of galectin-3 is the
chemotattraction of monocytes via a G-protein coupled receptor pathway and the role in
eosinophil rolling to sites of inflammation (Rao et al., 2007; Sano et al., 2000). Most of those
functions can only be performed by full length galectin-3 showing the importance of glycan
binding and oligomerisation of the protein (Markowska et al., 2010; Sano et al., 2000).
Different other biological activities are also depending on both N- and C-terminal domain
(Nieminen et al., 2005; Ochieng et al., 1998a; Sano et al., 2000; Sato et al., 2002; Yamaoka et
al., 1995). This proves the possibility of regulating galectin-3 function by protease cleavage
as mentioned in chapter 2.3.3.
Galectin-8 has been assigned to matricellular proteins which are able to promote cell
adhesion. CHO-cells on galectin-8 show similar binding kinetics as on fibronectin but differ
in their formation of cytoskeleton (Boura-Halfon et al., 2003). Moreover the binding to
galectin-8 triggers specific signalling cascades as Ras, MAPK and Erk pathway (Levy et al.,
2003). A physiological function in human might be the modulation of neutrophil function.
Galectin-8 promotes neutrophil adhesion by binding αM integrin and promatrix
metalloproteinase-9. Moreover superoxide production which is essentiell for neutrophil
function is triggered by galectin-8 C-terminal CRD (Nishi et al., 2003). Another galectin-8
function might be the promotion of angiogenesis as it was also shown for galectin-3.
Galectin-8 increases tube formation
in vitro
and angiogenesis
in vivo
in dependence of its
specific carbohydrate affinity at physiological concentrations. This regulatory function is at
least partially depending on CD 166 (Delgado et al., 2011).
6. Galectins in biomaterial research
As discussed in chapter 5.1 galectins can act pro- and antiadhesive which
in vivo
seems to be
mainly regulated by concentration and oligomerisation status of the galectins. In the context
of biomaterial research it is also of huge importance if the galectins are immobilised or
soluble presented. Immobilised galectins act mainly proadhesive as they crosslink the
surface they are immobilised on with glycosylated structures on the cell-membrane. Soluble
galectins can either facilitate or reduce adhesion for example to functionalised surfaces as
discussed for the
in vivo
situation in chapter 5.1 depending on concentration,
oligomerisation and cell type (respectively receptor availability on this cell type) (Elola et al.,
2007).
