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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Cell+Mol+Med
2010 ; 14
(6B
): 1569-93
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Podosome-like structures of non-invasive carcinoma cells are replaced in
epithelial-mesenchymal transition by actin comet-embedded invadopodia
#MMPMID19656240
Takkunen M
; Hukkanen M
; Liljeström M
; Grenman R
; Virtanen I
J Cell Mol Med
2010[Jun]; 14
(6B
): 1569-93
PMID19656240
show ga
Podosomes and invadopodia are actin-based structures at the ventral cell
membrane, which have a role in cell adhesion, migration and invasion. Little is
known about the differences and dynamics underlying these structures. We studied
podosome-like structures of oral squamous carcinoma cells and invadopodia of
their invasive variant that has undergone a spontaneous epithelial-mesenchymal
transition (EMT). In 3D imaging, podosomes were relatively large structures that
enlarged in time, whereas invadopodia of invasive cells remained small, but were
more numerous, degraded more extracellular matrix (ECM) and were morphologically
strikingly different from podosomes. In live-cell imaging, highly dynamic,
invadopodia-embedded actin tails were frequently released and rocketed through
the cytoplasm. Resembling invadopodia, we found new club-ended cell extensions in
EMT-experienced cells, which contained actin, cortactin, vinculin and MT1-matrix
metalloproteinase. These dynamic cell extensions degraded ECM and, in field
emission scanning electron microscopy, protruded from the dorsal cell membrane.
Plectin, alphaII-spectrin, talin and focal adhesion kinase immunoreactivities
were detected in podosome rings, whereas they were absent from invadopodia.
Tensin potentially replaced talin in invadopodia. Integrin alpha(3)beta(1)
surrounded both podosomes and invadopodia, whereas integrin alpha(v)beta(5)
localized only to invadopodia heads. Pacsin 2, in conjunction with filamin A, was
detected early in podosomes, whereas pacsin 2 was not found in invadopodia and
filamin A showed delayed accumulation. Fluorescence recovery after photobleaching
indicated faster reorganization of actin, cortactin and filamin A in podosomes
compared to invadopodia. In conclusion, EMT affects the invasion machinery of
oral squamous carcinoma cells. Non-invasive squamous carcinoma cells
constitutively organize podosomes, whereas invasive cells form invadopodia. The
club-ended cell extensions, or externalized invadopodia, are involved in ECM
degradation and maintenance of contact to adhesion substrate and surrounding
cells during invasion.