Cancer is the second most common cause of death in Switzerland. There are various reasons why in the age of cutting-edge medicine it is still difficult to fashion a cure for this disease. A tumor may, for instance, comprise of different tumor cell subpopulations, each of which has its own profile and reacts differently when subjected to therapy, or not. Additionally, the cancer cells and the healthy cells in the body interact and communicate with one another. How a tumor then actually develops and whether metastases form simply relies on which signals a tumor cell receives from its surrounding environment.
With the development of a new method the team led by Prof. Bernd Bodenmiller from the Institute of Molecular Life Sciences at the University of Zurich, in collaboration with ETH Zurich and University Hospital Zurich, has succeeded in comprehensively profiling and visualizing tumor cells from patient samples. This promising new method has since been published in Nature Methods.
In an effort to determine a tumor's cell profile, its environment relationships and the circuit structure within and in between cells is a highly multifaceted enterprise. This is because the biomarkers, i.e. the particular molecules of the various cell types and their circuits, have to be measured in their spatial relationships.
"With our method it is possible to obtain a comprehensive picture using a novel imaging technique that currently can simultaneously record 32, and in the near future more than one hundred biomarkers. Furthermore, thanks to state-of-the-art imaging the information about the cells' neighborhood relationships is kept and their direct impact on the cellular switch and control circuits can be visualized,” explains study coordinator, Bernd Bodenmiller.
The new method is predicated on techniques which are already routinely applied and used in hospitals, with two significant innovations. First, the biomarkers are visualized using pure metal isotopes instead of dyes. To accomplish this, biomarkers are set on very thin tissue sections are labelled with antibodies. The antibodies are joined to the pure metal isotopes. Then tiny pieces of tissue are extracted with a laser system developed by Prof. Detlef Günther from the ETH Zurich, and the metal isotopes of the pieces are measured with a mass spectrometer which can determine the mass and quantity of the individual metal isotopes.
"This trick gets round the problem of the limited number of colours in the analysis of biological samples," noted Bodenmiller.
Secondly, information about the cells, and their control circuits, is no longer qualitative. With the new measurement method it is possible to accurately determine which cells experience what effect and to what extent. In this way the weak points of the control system can be pinpointed and this helps in the development of new therapeutic approaches and methods. According to Bodenmiller, this is the reason on why it is becoming increasingly important to understand these interactions for diagnosis and therapy.
The preliminary measurement results of the new biomarker technique for breast cancer have shown the heterogeneity of tumors. As a result of major growth, some tumors suffer from oxygen shortage on the inside, while others mistreat the body's own immune cells to further their growth. Cell-cell interaction and cell location in the center or on the edges of the tumor also have a vital impact. One thing is certain: no tumor is like any other and Bodenmiller believes that treatment should be based on this principle. For their next phase, his research team wishes to use the new measurement method to explore the roles played by control circuits and cell communication in metastasis formation.
