Epigenetic changes in tumor cells

Miguel Vizoso, a postdoc in the group of Jacco van Rheenen at the Hubrecht Institute (KNAW), has received an EMBO fellowship for his research project ‘DNA methylation insights into cancer cell plasticity by intravital imaging’. This fellowship will enable him to spend two years studying the epigenetic dynamics of tumor cells. In the future, this might help us develop new treatments for cancer.

Tumor cell diversity
In a tumor, not allake place in the cell require a different set of genes to be turned ‘on’. Previous research has shown that some cells in a tumor change their identity to be able to leave the primary tumor and form a metastasis somewhere else. To be able to change their identity, the cells need to change which genes are turned ‘on’ and ‘off’. If we can find out how this identity change is initiated, by looking at changes in these epigenetic marks, we might be able to develop treatments that block this identity change and thereby stop the tumor from metastasizing.

Epigenetic research in tumors until now
Epigenetic marks in tumors have been studied in the past, but usually this is done on a mix of cells from a tumor, and for instance by comparing a primary tumor with a metastasized tumor. This kind of research provides very useful information, but does not reveal information on individual cells within the tumor, or on the development of the tumor over time. If we want to find out which changes enable certain cells to leave the tumor and travel through the body, we need different techniques.

Studying epigenetic dynamics
In his research, Miguel combines different techniques to gain more insight into the epigenetic changes in individual tumor cells. One of these techniques is intravital microscopy, a specialty of the Van Rheenen group. Using this technique, the van Rheenen group can visualize the behavior of individual cells for several weeks, during the development of a tumor in living mice. Miguel is going to combine this technique with a method that enables him to look at epigenetic marks in specific regions in the DNA. Under the microscope he will then see fluorescence in cells that do not carry the epigenetic mark on the specific DNA region, and he will not see fluorescence in cells that do carry the mark. This will enable him to find out whether cells that detach from the tumor carry epigenetic marks on regions of the DNA that we know are important for tumor development.

The future
There are already treatments that can change epigenetic marks on the DNA, but the problem is that they change the mark in the entire DNA of a cell, turning the entire DNA ‘on’ or ‘off’. The disadvantage of this is that this creates many unwanted effects in the cells. The ultimate goal is to develop treatments that target only specific regions in the DNA and turn these regions ‘on’ or ‘off’, to block metastasis. To be able to develop these treatments we need to know which regions to turn ‘on’ or ‘off’. And that is exactly what Miguel’s research is going to teach us. It will take a long time until we can develop such treatments, but this research will bring us another step closer.

Prof. Dr. Jacco van Rheenen is group leader at the Hubrecht Institute (KNAW) and Professor of Intravital Microsopy at the University Medical Center Utrecht and University Utrecht.