title: Cancer cell invasion and EMT marker expression: a three-dimensional study of the human cancer-host interface.
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.
authors: Institute of Pathology, University Medical Centre, Freiburg, Germany; Comprehensive Cancer Centre, Freiburg, Germany.
authors: P
authors: P
authors: Bronsert
authors: K
authors: K
authors: Enderle-Ammour
authors: M
authors: M
authors: Bader
authors: S
authors: S
authors: Timme
authors: M
authors: M
authors: Kuehs
authors: A
authors: A
authors: Csanadi
authors: G
authors: G
authors: Kayser
authors: I
authors: I
authors: Kohler
authors: D
authors: D
authors: Bausch
authors: J
authors: J
authors: Hoeppner
authors: U T
authors: UT
authors: Hopt
authors: T
authors: T
authors: Keck
authors: E
authors: E
authors: Stickeler
authors: B
authors: B
authors: Passlick
authors: O
authors: O
authors: Schilling
authors: C P
authors: CP
authors: Reiss
authors: Y
authors: Y
authors: Vashist
authors: T
authors: T
authors: Brabletz
authors: J
authors: J
authors: Berger
authors: J
authors: J
authors: Lotz
authors: J
authors: J
authors: Olesch
authors: M
authors: M
authors: Werner
authors: U F
authors: UF
authors: Wellner
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: cancer cell invasion; epithelial-mesenchymal transition; human adenocarcinoma; three-dimensional reconstruction; tumour budding