Cluster of Excellence –
University of Freiburg

Modelling epithelial cancers for targeting carcinogenesis and progression

Dr. rer. nat. Christiane Fichter, Prof. Dr. Silke Laßmann (Institute of Clinical Pathology, University Medical Center Freiburg)

Collaborative Project with PD Dr. Oliver Schilling (Institute for Molecular Medicine, University of Freiburg)

 

Cancers develop in complex tumor microenvironments consisting of various cell types such as macrophages, immune cells, angiogenic cells or fibroblasts. These different cell types not only support sustained tumor growth, but also cancer cell invasion and metastasis and thereby contribute to cancer progression and poor prognosis for cancer patients.

Cancer associated fibroblasts (CAFs) are distinct from normal fibroblasts and are often present in high numbers in the tumor microenvironment. In contrast to normal fibroblasts, CAFs are more potent to promote tumorigenesis and metastasis. In this project, we study the interaction of cancer cells with normal or cancer associated fibroblasts in the two major histotypes of esophageal cancer - esophageal squamous cell carcinoma and esophageal adenocarcinoma. Thereby, three-dimensional organotypic cultures allow co-cultivation of epithelial cancer cells and fibroblasts to obtain novel insights in tumor-stroma interactions and their effects on cancer cell motility and invasion. Functional in vitro analyses and in situ analyses of human esophageal cancer tissue specimens further support the project.

 

 

Three-dimensional organotypic cultures (OTCs) are a kind of tissue engineering and allow the in vitro reconstruction of e.g. esophageal squamous cell carcinomas (a-d) or esophageal adenocarcinomas (e-h). In these OTCs, epithelial cells grow on a collagen/Matrigel matrix organized by fibroblasts. Esophageal squamous cell carcinoma cells are positive for the epithelial marker CK5/6 (b, f) whereas esophageal adenocarcinoma cells are positive for CK7 (c, g). This distinguishes the epithelial cancer cells from Vimentin positive fibroblasts (d, h). Epithelial cancer cells and fibroblasts seem to interact and this might also promote cancer cell invasion.