Targets in the microenvironment of rectal cancer: A focus on angiogenic growth factors and chemokines

Cancer cells interact with each other, and with cells of the tumor microenvironment. This coincides with the production of numerous soluble factors which can stimulate cancer cell growth and migration. In addition the tumor microenvironment can facilitate cancer cells to escape the effect of anticancer treatment. Understanding how the cross-talk between cancer and non-cancer cells in the tumor microenvironment mediates disease progression and resistance to treatment can potentially help to define novel and more successful treatments. In this thesis we therefore studied vessel growth factors and migration factors in metastatic rectal cancer. These patients received radiotherapy for their rectal cancer and systemic therapy including an antibody bevacizumab, that binds to the vessel growth stimulation factor VEGF-A. This treatment allowed subsequent surgical removal of the tumor in the rectum and the metastases in the liver and lungs in 72% of the patients. By examining the protein expression profile of growth and migration factors in rectal cancer cells and neighboring connecting non-cancer cells before and after the aforementioned therapy, we identified placental growth factor (PlGF) and the chemokine ligand CXCL12/ chemokine receptor CXCR4 pair as potential drug targets for rectal cancer therapy.