Thesis defence Evelyne Beerling

Evelyne Beerling from the Van Rheenen group defended her thesis “Intravital imaging of cancer – Visualizing the bad guys”, in which she studies how tumors metastasize, on June 1st.

Even though we have gained a wealth of knowledge over the past years, cancer is still one of the most occurring causes of death in the Western world. For most patients it is not the primary tumor that is fatal, but the metastases. These metastases develop because some tumor cells leave the primary tumor and nest in other organs. It is important to understand how these ‘bad guys’ are able to leave the primary tumor, travel through the circulatory system and grow a new tumor in a different organ, so that new therapies can target these processes.

During her PhD Beerling studied these ‘bad guys’ and their behavior in their natural setting. This type of research is often done on tumor cells in plastic petri dishes, but the disadvantage of this is that the 3D structure, in which a tumor exists in the body, is not present in a petri dish. Therefore Beerling studied tumors in living mice. A small imaging window is placed in the skin of these mice, to be able to look at the tumor with a microscope.

‘Bad guys’ change their identity to form metastases

Beerling studied two different types of tumors: pancreatic tumors and breast tumors. By studying these tumors she discovered that the cells that leave the primary tumor change their identity. Primary pancreatic and breast tumors consist of epithelial cells; cells that are strongly attached to each other. They contain a molecule called E-cadherin that enables them to stick to each other. The cells that leave the primary tumor lose their E-cadherin molecules and start to resemble mesenchymal cells. Mesenchymal cells are cells that do not attach to each other and this enables them to travel through the surrounding tissue. In addition, she discovered that the cells that have left the tumor and start a new tumor in a different organ change their identity back to epithelial cells and make new E-cadherin molecules. Subsequently they form a new tumor that consists of strongly attached cells. These two transition steps, from epithelial cells to mesenchymal cells and back, are important targets for new treatments. If these processes could be slowed down or even stopped, tumors cannot metastasize anymore and this could substantially increase the chance of survival for cancer patients.

Chemotherapy

Lastly, Beerling also discovered that a widely used chemotherapeutic, to which only half of the patients responds, causes a different response in mice with a tumor than in tumor cells in a petri dish. This discovery shows that understanding the mechanism of a certain treatment is incredibly important, so that we can better predict which patients will respond to the treatment, and which patients will not.