Portal de Periódicos da CAPES

Cancer cell invasion and EMT marker expression: a three-dimensional study of the human cancer-host interface

2014; Volume: 234; Issue: 3 Linguagem: Inglês

10.1002/path.4416

1096-9896

Peter Bronsert, Kathrin Enderle-Ammour, M Bader, Sylvia Timme, Markus Kuehs, Ágnes Csanádi, Gian Kayser, Ines Köhler, Dirk Bausch, Jens Hoeppner, UT Hopt, Tobias Keck, Elmar Stickeler, Bernward Passlick, Oliver Schilling, CP Reiss, Yogesh K. Vashist, Thomas Brabletz, Judith Berger, Johannes Lotz, Janine Olesch, Martin Werner, Ulrich F. Wellner,

FOXO transcription factor regulation

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.