| Development of colorectal cancer is characterized by accumulation of somatic mutations within tumor cells. In addition, the tumorigenic process is influenced by interactions between epithelial tumor cells and non-epithelial stromal cells, affecting processes like angiogenesis, immune surveillance, and metastasis. We aim to characterize the effects of stromal cells from hematopoietic origin on initiation and progression of colorectal cancer. The effects of somatic mutations in neoplastic cells on tumor microenvironment were evaluated by quantitative measurements of H&E-stained sections using a panel of colon carcinomas whose chromosomal aberrations were previously characterized by array-CGH. Two specific somatic changes that affect stroma composition were identified, i.e. loss of 1p36 and loss of 9q34. The effects of hematopoietic cells on colon tumor development are investigated using bone marrow transfer experiments. The hematopoietic system of acceptor mice is replaced by GFP-transgenic hematopoietic donor cells, and we are currently studying the kinetics of their migration into normal colon tissue and colon tumors. These studies indicate that specific somatic changes in colon cancer cells affect tumor-stroma interaction and thereby tumor morphology, and allow us to investigate the effects of (genetically modified) hematopoietic stromal cells on colon tumor development using a mouse model of colon cancer. |
