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Review
. 2008 Sep;130(3):481-94.
doi: 10.1007/s00418-008-0464-1. Epub 2008 Jul 22.

Molecular and pathological signatures of epithelial-mesenchymal transitions at the cancer invasion front

Affiliations
Review

Molecular and pathological signatures of epithelial-mesenchymal transitions at the cancer invasion front

Olivier De Wever et al. Histochem Cell Biol. 2008 Sep.

Abstract

Reduction of epithelial cell-cell adhesion via the transcriptional repression of cadherins in combination with the acquisition of mesenchymal properties are key determinants of epithelial-mesenchymal transition (EMT). EMT is associated with early stages of carcinogenesis, cancer invasion and recurrence. Furthermore, the tumor stroma dictates EMT through intensive bidirectional communication. The pathological analysis of EMT signatures is critically, especially to determine the presence of cancer cells at the resection margins of a tumor. When diffusion barriers disappear, EMT markers may be detected in sera from cancer patients. The detection of EMT signatures is not only important for diagnosis but can also be exploited to enhance classical chemotherapy treatments. In conclusion, further detailed understanding of the contextual cues and molecular mediators that control EMT will be required in order to develop diagnostic tools and small molecule inhibitors with potential clinical implications.

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Figures

Fig. 1
Fig. 1
Schematic representation of EMT markers. Upregulated factors implicated in cytoskeletal changes and the mesenchymal phenotype (green side) and repressed markers (red side) implicated in the maintenance of the epithelial phenotype. See text for more details
Fig. 2
Fig. 2
Conditional expression of Snail stimulates invasion. Light microscopy of H&E stained paraffin sections from doxycyclin-inducible 105 DLD-1TR21-hSnailMyc/His colon cancer cells that were seeded on a layer of collagen type I (1 mg/ml) in the absence (A and B) or presence (C and D) of doxycyclin; fixation was after 14 days culture with medium refreshments every 48 h. Arrows are invasive DLD-1 cells. Scale bar = 50 μm
Fig. 3
Fig. 3
Histology of basal cell carcinoma. Hematoxylin and eosin staining of a basal cell carcinoma showing the collective invasion of epithelial cancer cells into the extracellular matrix (arrows, panel A). Single cancer cells detached from the tumor mass and showing traits of epithelial–mesenchymal transition are indicated by arrows (panel B). Stromal (myo)fibroblasts are indicated by arrowheads. Scale bars = 50 μm

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