Document Detail

Podosome-like structures of non-invasive carcinoma cells are replaced in epithelial-mesenchymal transition by actin comet-embedded invadopodia.
MedLine Citation:
PMID:  19656240     Owner:  NLM     Status:  MEDLINE    
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.
Minna Takkunen; Mika Hukkanen; Mikko Liljeström; Reidar Grenman; Ismo Virtanen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-28
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  14     ISSN:  1582-4934     ISO Abbreviation:  J. Cell. Mol. Med.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-07-30     Completed Date:  2010-11-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  1569-93     Citation Subset:  IM    
Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland.
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MeSH Terms
Actins / metabolism*
Cell Adhesion / drug effects
Cell Line, Tumor
Cell Membrane / drug effects,  metabolism,  ultrastructure
Cell Movement / drug effects
Cell Shape / drug effects
Epithelium / drug effects,  metabolism,  pathology*
Extracellular Matrix / metabolism
Fluorescence Recovery After Photobleaching
Integrins / metabolism
Mesoderm / drug effects,  metabolism,  pathology*
Neoplasm Invasiveness
Neoplasm Proteins / metabolism
Neoplasms / metabolism,  pathology*
Pseudopodia / drug effects,  pathology*,  ultrastructure
Tubulin Modulators / pharmacology
Wound Healing / drug effects
Reg. No./Substance:
0/Actins; 0/Integrins; 0/Neoplasm Proteins; 0/Tubulin Modulators
Erratum In:
J Cell Mol Med. 2010 Aug;14(8):2185

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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