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

被引:287
作者
Bronsert, P. [1 ,4 ]
Enderle-Ammour, K. [1 ]
Bader, M. [1 ]
Timme, S. [1 ]
Kuehs, M. [1 ,4 ]
Csanadi, A. [1 ]
Kayser, G. [1 ]
Kohler, I. [1 ]
Bausch, D. [2 ,3 ]
Hoeppner, J. [2 ]
Hopt, U. T. [2 ]
Keck, T. [2 ,3 ]
Stickeler, E. [4 ,5 ,6 ,7 ]
Passlick, B. [8 ]
Schilling, O. [4 ,10 ]
Reiss, C. P. [9 ]
Vashist, Y. [11 ]
Brabletz, T. [2 ,4 ,5 ,6 ]
Berger, J. [12 ]
Lotz, J. [12 ]
Olesch, J. [12 ]
Werner, M. [1 ,4 ,5 ,6 ]
Wellner, U. F. [2 ,3 ]
机构
[1] Univ Med Ctr, Inst Pathol, Freiburg, Germany
[2] Univ Med Ctr, Clin Gen & Visceral Surg, Freiburg, Germany
[3] Univ Clin, Surg Clin, Lubeck, Germany
[4] Ctr Comprehens Canc, Freiburg, Germany
[5] German Canc Consortium DKTK, Heidelberg, Germany
[6] Canc Res Ctr DKFZ, Heidelberg, Germany
[7] Univ Med Ctr, Clin Gynecol, Freiburg, Germany
[8] Univ Med Ctr, Clin Thorac Surg, Freiburg, Germany
[9] Univ Hosp, Dept Urol, Hamburg Eppendorf, Germany
[10] Univ Freiburg, Inst Mol Med & Cell Res, Freiburg, Germany
[11] Univ Hamburg Hosp, Dept Gen Surg, Hamburg, Germany
[12] Fraunhofer MEVIS, Project Grp Image Registrat, Lubeck, Germany
关键词
cancer cell invasion; epithelial-mesenchymal transition; tumour budding; human adenocarcinoma; three-dimensional reconstruction; EPITHELIAL-MESENCHYMAL TRANSITION; CARCINOMA INVASION; PROGNOSTIC VALUE; TUMOR; RECONSTRUCTION; METASTASIS; PLASTICITY; MIGRATION; SLUG;
D O I
10.1002/path.4416
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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 (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
引用
收藏
页码:410 / 422
页数:13
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