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Spatial organization of proteins in metastasizing cells
Author(s) -
Rönnlund Daniel,
Gad Annica K. B.,
Blom Hans,
Aspenström Pontus,
Widengren Jerker
Publication year - 2013
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.22304
Subject(s) - vimentin , cytoskeleton , microbiology and biotechnology , sted microscopy , adhesion , intermediate filament , cell adhesion , matrix (chemical analysis) , cell , fibroblast , focal adhesion , chemistry , biophysics , biology , immunology , in vitro , optics , stimulated emission , immunohistochemistry , biochemistry , signal transduction , laser , physics , organic chemistry , chromatography
The ability of tumor cells to invade into the surrounding tissue is linked to defective adhesive and mechanical properties of the cells, which are regulated by cell surface adhesions and the intracellular filamentous cytoskeleton, respectively. With the aim to further reveal the underlying mechanisms and provide new strategies for early cancer diagnostics, we have used ultrahigh resolution stimulated emission depletion (STED) microscopy as a means to identify metastasizing cells, based on their subcellular protein distribution patterns reflecting their specific adhesive and mechanical properties. We have compared the spatial distribution of cell‐matrix adhesion sites and the vimentin filamentous systems in a matched pair of primary, normal, and metastatic human fibroblast cells. We found that the metastatic cells showed significantly increased densities and more homogenous distributions of nanoscale adhesion‐related particles. Moreover, they showed an increase in the number but reduced sizes of the areas of cell‐matrix adhesion complexes. The organization of the vimentin intermediate filaments was also found to be significantly different in the metastasizing cells, showing an increased entanglement and loss of directionality. Image analysis procedures were established, allowing an objective detection and characterization of these features and distinction of metastatic cells from their normal counterparts. In conclusion, our results suggest that STED microscopy provides a novel tool to identify metastasizing cells from a very sparse number of cells, based on the altered spatial distribution of the cell‐matrix adhesions and intermediate filaments.