Tumor-stroma interaction in human cancer
The majority of human tumours are carcinomas (~90%), which develop from epithelial cells by accumulation of mutations, and account for the majority of cancer deaths per year. In carcinomas epithelial structures are always interwoven with fibroblasts, endothelial cells, pericytes and inflammatory cells. These mesenchymal cells constitute the so-called tumour stroma.
There is strong evidence for beneficial stromal influence on tumour development from experimental models. How the tumor stroma is involved in cancer initiation, invasion and metastasis is extensively studied, but so far less clear. Determining the stromal impact on tumour cells, and the reciprocal influence of malignant epithelial cells on the stroma at the molecular level will help to better understand cancer development.
We are specifically interested in the crosstalk between tumour cells and cancer associated fibroblasts (CAFs) and put our focus on colon cancer to determine novel molecular mechanisms in the crosstalk between these cell types. We developed a state of the art three-dimensional co-culture model, which recapitulates many aspects of carcinomas in vivo, and identified well known and novel pathways, which are activated if carcinoma cells interact with CAFs. We focus on the modulation of the wnt/beta-catenin and the PI3K/Akt/mTOR signalling pathways in tumour cell –stromal fibroblast crosstalk and its implications for malignancy.