Cancer cell invasion and EMT marker expression: a three‐dimensional study of the human cancer–host interface |
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| Authors: | P Bronsert K Enderle‐Ammour M Bader S Timme M Kuehs A Csanadi G Kayser I Kohler D Bausch J Hoeppner UT Hopt T Keck E Stickeler B Passlick O Schilling CP Reiss Y Vashist T Brabletz J Berger J Lotz J Olesch UF Wellner |
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| Affiliation: | 1. Institute of Pathology, University Medical Centre, , Freiburg, Germany;2. Comprehensive Cancer Centre, , Freiburg, Germany;3. Clinic for General and Visceral Surgery, University Medical Centre, , Freiburg, Germany;4. Clinic for Surgery, University Clinic, , Lübeck, Germany;5. German Cancer Consortium (DKTK) and Cancer Research Centre (DKFZ), , Heidelberg, Germany;6. Clinic for Gynecology, University Medical Centre, , Freiburg, Germany;7. Clinic for Thoracic Surgery, University Medical Centre, , Freiburg, Germany;8. Institute of Molecular Medicine and Cell Research, University of Freiburg, , Germany;9. Department of Urology, University Hospital, , Hamburg‐Eppendorf, Germany;10. Department of General Surgery, University Hospital, , Hamburg‐Eppendorf, Germany;11. Fraunhofer MEVIS, Project Group Image Registration, , Lübeck, Germany |
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| Abstract: | Cancer cell invasion takes place at the cancer–host interface and is a prerequisite for distant metastasis. The relationships between current biological and clinical concepts such as cell migration modes, tumour budding and epithelial–mesenchymal transition (EMT) remains unclear in several aspects, especially for the 'real' situation in human cancer. We developed a novel method that provides exact three‐dimensional (3D) information on both microscopic morphology and gene expression, over a virtually unlimited spatial range, by reconstruction from serial immunostained tissue slices. Quantitative 3D assessment of tumour budding at the cancer–host interface in human pancreatic, colorectal, lung and breast adenocarcinoma suggests collective cell migration as the mechanism of cancer cell invasion, while single cancer cell migration seems to be virtually absent. Budding tumour cells display a shift towards spindle‐like as well as a rounded morphology. This is associated with decreased E‐cadherin staining intensity and a shift from membranous to cytoplasmic staining, as well as increased nuclear ZEB1 expression. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
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| Keywords: | cancer cell invasion epithelial– mesenchymal transition tumour budding human adenocarcinoma three‐dimensional reconstruction |
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