Biology Reference
In-Depth Information
Lamellipodia
Filopodia
MT1-MMP
MMP-2
MMP-9
Podosomes
Invadopodia
CD44
Fig. 7.3 Cell membrane migration/invasion structures involving MMP matrix proteolysis and
remodeling. The schematic depicts major types of cell membrane structures implicated in cell
migration and invasion, i.e., sheet-like lamellipodia, rod-like filopodia, shallow podosomes, and
deeper penetrating invadopodia. The association of these structures with MMPs is highlighted by
the cell surface tethered MT1-MMP alone or in complex with CD44 or by focalized binding of
secreted MMP-2 and MMP-9 to MT1-MMP and CD44, respectively
with the crucial elements of migration machinery such as integrins, F-actin, cor-
tactin, and RhoGTPases (Chen and Wang
1999
; Wolf et al.
2007
; Wolf and Friedl
2009
; Yilmaz and Christofori
2009
). In the flat, sheet-like lamellipodia regarded as
the main organelle for cell locomotion, MT1-MMP was identified directly bound
via its hemopexin-like domain to CD44, mediating its proteolytic cleavage and
stimulating cell migration due to disrupted hyaluronan-mediated adhesion (Mori
et al.
2002
). Matrix proteolysis mediated by MT1-MMP and MMP-2 and MMP-9
gelatinases has been linked to the filopodia, rod-like cell extensions, the presence of
which correlates with the invasiveness of angiogenic endothelial (De Smet et al.
2009
) and metastatic cells (Coopman et al.
1998
). The podosomes found in non-
transformed but highly migratory cells are believed to be formed when cell adhe-
sion junctions and matrix should be degraded concomitantly (Linder
2009
; Yilmaz
and Christofori
2009
). Not surprisingly, membrane-bound MT1-MMP has been
implicated in such coordinated proteolysis (Linder
2009
), e.g., by dendritic cells
(West et al.
2008
) or endothelial cells (Tatin et al.
2006
; Varon et al.
2006
). In
addition to MT1-MMP, both MMP-2 and MMP-9 have also been localized to
podosomes in different cell types including activated endothelial cells (Tatin
et al.
2006
; Varon et al.
2006
; Wang et al.
2009
).
Invadopodia are formed mostly by invading carcinoma cells and are consid-
ered the transformed counterparts of podosomes (Yamaguchi et al.
2005
; Linder
2007
,
2009
). These cell structures play an important role in directional tumor
invasion and also in tumor cell intravasation into blood and lymphatic vessels
and tumor cell extravasation at secondary sites (Yilmaz and Christofori
2009
).
