Background

Tumor development is characterized by accumulation of somatic mutations in oncogenes and tumor suppressor genes, genetic changes that function cell-autonomously and are the driving force behind clonal expansion of neoplastic cells. In addition, within the tumor microenvironment interactions between neoplastic cells and stromal cells like macrophages, T-cells, endothelial cells and fibroblasts affect processes like immune surveillance, angiogenesis, and metastasis. This research project focuses on the influence of hematopoietic cells on colon tumor development.

Aim

Based on previous work using microarray expression analysis we have obtained a list of genes that may affect colon tumor development through their function in hematopoietic cells. One of these genes will be selected for further characterization.

Plan of work

• Determine by what subset of hematopoietic cells the gene of interest is expressed (FACS analysis / immunohistochemical staining of blood smears).
• Determine whether its expression in human / mouse colon (tumors) is restricted to hematopoietic cells, or is also expressed by epithelial cells (immunohistochemistry / immunofluorescence).
• Determine whether expression levels of this gene in blood of colon cancer 'susceptible' individuals differs from colon cancer 'resistant' individuals (RealTime-quantitative PCR).
• In case of promising results: Investigate the effect of downmodulation of this gene in hematopoietic cells on expression of genes by colon cancer cell lines (cocultures of hematopoietic cells with tumor cells, knockdown by siRNA).

More information

For more information please contact  dr. R.J.A. Fijneman