title: Spatial organization of proteins in metastasizing cells.
abstract: 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.
authors: Department of Experimental Biomolecular Physics/Applied Physics, KTH-Royal Institute of Technology, AlbaNova University Center, Stockholm, Sweden.
authors: Daniel
authors: D
authors: Rönnlund
authors: Annica K B
authors: AK
authors: Gad
authors: Hans
authors: H
authors: Blom
authors: Pontus
authors: P
authors: Aspenström
authors: Jerker
authors: J
authors: Widengren
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D021982:Cell-Matrix Junctions / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008853:Microscopy / Q000379:methods*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000032:analysis* / Q000378:metabolism
chemical_list: D014746:Vimentin
keywords: STED microscopy; cancer; cell adhesion; diagnostics; image analysis; metastasis; vimentin