Whether a tumour develops from individual cancer cells and whether metastases are formed depends on many factors in the affected tissue. A greater understanding of a tumour’s complex switch and control circuits could help to combat cancer in a more targeted fashion. Researchers at the University of Zurich have come up with an imaging method that is able to simultaneously visualize a previously unachieved number of factors involved in cancer.
Cancer is the second most common cause of death in Switzerland. There are many reasons why in the era of cutting-edge medicine it is still difficult to cure this disease.
A tumour may, for instance, consist of different tumour cell subpopulations, each of which has its own profile and responds differ-ently to therapy – or not. Furthermore, the cancer cells and the healthy cells in the body interact and communicate with one another.
How a tumour then actually develops and whether metastases form depends on which signals a tumour cell receives from its environment. With the development of a new method the team around Prof. Bernd Bodenmiller from the Institute of Molecular Life Sciences at the University of Zurich – in cooperation with ETH Zurich and University Hospital Zurich – has suc-ceeded in comprehensively profiling and visualizing tumour cells from patient samples. This promising method has now been published in “Nature Methods”.
New imaging method – major opportunity
Setting out to determine a tumour’s cell profile, its neighbourhood relationships and the circuit struc-ture within and in between cells is a highly complex endeavour. This is because the biomarkers, i.e. the specific 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”, explains Bernd Bodenmiller, the study coordinator. Furthermore, thanks to state-of-the-art imaging the information about the cells’ neighbourhood relationships is kept and their direct impact on the cellular switch and control circuits can be visualised.
The new technique is based on methods which are already routinely used in hospitals – with two im-portant innovations. First, the biomarkers are visualised using pure metal isotopes instead of dyes. To do so, biomarkers on very thin tissue sections are labelled with antibodies. The antibodies are cou-pled to the pure metal isotopes.
Then tiny pieces of tissue are removed with a laser system devel-oped 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 sam-ples”, comments Bodenmiller.
Secondly, information about the cells, and their control circuits, is no longer qualitative. With the new measurement method it is possible to precisely determine which cells experience what effect and to which extent. In this way the weak points of the control system can be pinpointed and this helps in the development of new therapeutic approaches. This is the reason, so Bodenmiller, why it is becoming increasingly important to understand these interactions for diagnosis and therapy.
Customised treatment is the goal
The initial measurement results of the new biomarker technique for breast cancer have revealed the heterogeneity of tumours. As a consequence of major growth, some tumours suffer from oxygen defi-ciency on the inside, other misuse the body’s own immune cells to drive their growth. Cell-cell interac-tion and cell location in the centre or on the edges of the tumour also have a decisive influence. One thing is clear: no tumour is like any other and Bodenmiller believes that treatment should reflect this. In a next step his research team wishes to use the new measurement method to explore the roles played by control circuits and cell communication in metastasis formation.
Charlotte Giesen, H. A. O. Wang, Denis Schapiro, Nevena Zivanovic, Andrea Jacobs, Bodo Hatten-dorf, Peter J Schüffler, Daniel Grolimund, Joachim M Buhmann, Simone Brandt, Zsuzsanna Varga, Peter J. Wild, Detlef Günther & Bernd Bodenmiller. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nature Methods, March 2014. DOI:10.1038/nmeth.2869
Prof. Bernd Bodenmiller
Institute of Molecular Biology
University of Zurich
Tel: +41 (0)44 635 31 28
University of Zurich
Tel. +41 44 634 44 39
Email: bettina. firstname.lastname@example.org
Bettina Jakob | Universität Zürich
Breaking through a double wall with a sledgehammer
29.06.2015 | Max-Planck-Institut für Entwicklungsbiologie
Lean but sated: Molecular Switch for a Healthy Metabolism discovered
29.06.2015 | Leibniz-Institut für Altersforschung - Fritz-Lipmann-Institut e.V. (FLI)
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...
A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...
The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...
On June 23, the second Sentinel mission was launched from the space mission launch center in Kourou. A critical component of Aachen is on board. Researchers at the Fraunhofer Institute for Laser Technology ILT and Tesat-Spacecom have jointly developed the know-how for space-qualified laser components. For the Sentinel mission the diode laser pump module of the Laser Communication Terminal LCT was planned and constructed in Aachen in cooperation with the manufacturer of the LCT, Tesat-Spacecom, and the Ferdinand Braun Institute.
After eight years of preparation, in the early morning of June 23 the time had come: in Kourou in French Guiana, the European Space Agency launched the...
(Nano)islands that slide freely on a sea of copper, but when they become too large (and too dense) they end up getting stuck: that nicely sums up the system...
25.06.2015 | Event News
16.06.2015 | Event News
11.06.2015 | Event News
29.06.2015 | Life Sciences
29.06.2015 | Life Sciences
29.06.2015 | Physics and Astronomy