Study of individual cells reveals unexpected differences in colon cancer cells

In DTCT, the German Cancer Research Center (DKFZ) in Heidelberg is a long-term center of excellence in Germany with oncology well-known partner sites.

In colorectal cancer, two genes are most often mutated, KRAS and BRAF. Genetic changes in KRAS or BRAF activate the same signal path in both cases. In response to these signals, the cells begin to be uncontrolled.

So far, doctors have believed that changes in these two genes lead to similar growth signals in all cancer cells. However, this assumption seems to be wrong, as scientists under the guidance of Markus Morkel and Nilsa Blüthgena from the German Cancer Consortium (DKTK) at Charité – Universitätsmedizin Berlin have now thoroughly investigated.

"We were surprised that KRAS gene mutations in colon cancer caused cellular response only in the cancer cell, but not in others." The difference seems to be in cellular differentiation, that is to try to get cancer cells in a certain type of cell. The mutated BRAF gene, on the other hand, has triggered growth signals in all cellular conditions, Morkel says, summing up the important finding of the study. The KRAS signal path plays an important role in the cell division and is therefore a central starting point for targeting colorectal cancer.

For tumors with altered KRAS – this affects almost half of all cases of colon cancer in Germany – there is still no targeted therapeutic option. New research results are therefore very important for optimizing long-term treatment of colorectal cancer. Since colon cancer with mutated KRAS only a part of the cell transmits modified growth signals, the tumor is still highly heterogeneous. Therefore, it is very difficult to access therapies.

"Our findings suggest that future therapies must be combined to synchronize colon cancer cells, that is, to bring them into a unique state." In addition to fundamental scientific importance, this discovery may also be clinically relevant, as our research can help develop future targeted combined therapies, "Blüthgen classifies the importance of research data.

These results enabled analysis of individual cells. With their help, scientists are now able to detect the differences between thousands of individual tissue cells, such as tissue. As the intestinal tissue is specifically explored. In addition, Morkel and colleagues used the so-called " Organic technology. Particularly related to this: the cancer tissue cells obtained from the surgical material are transformed into three-dimensional structures in the laboratory. In addition, researchers used computer simulations to understand where signal processing could be blocked by the cell itself. According to research findings, cancer cells may switch information chains to uncontrolled cell division or exclude at certain points. This also explains the frequent observation that certain signal pathways within the colon tumor are not active in all, but only in the part of cancer cells – and this again affects the possibility of treating the tumor.

Raphael Brandt, Thomas Sell, Mareen Lüthen, Florian Uhlitz, Bertram Klinger, Pamela Riemer, Claudia Giesecke-Thiel, Silvia Schulze, Ismail Amr El-Shimy, Desiree Kunkel, Beatrix Fauler5, Thorsten Mielke, Norbert Mages, Bernhard G. Herrmann, Christine Sers, Nils Blüthgen & Markus Morkel: Differential activation of ERK dependent on cell type oncogeneous KRAS in colorectal carcinomas and intestinal epithelium.
Nature Communications 2019; https://doi.org/10.1038/s41467-019-10954-y

Image is available at:
https://www.dkfz.de/de/presse/pressemitteilungen/2019/bilder/darmepithel-kultur.jpg
Source: Markus Morkel / Charité – Universitätsmedizin Berlin

Description: The organoid intestine grows in a three-dimensional matrix and displays cancer-induced cancer (ERK) signal as green fluorescence in the nucleus. Cell cryptate cell nuclei (right) exhibit high activity, whereas differentiated epithelial cells (left) show low activity.

Notice on the use of image media for press releases
Use is free. The German Cancer Research Center (DKFZ) allows for one-time use in reporting on the topic of publicity or in general about DKFZ. Please quote as a picture of the loan: "Source: Markus Morkel / Charité – Universitätsmedizin Berlin".
Transfer of image material to third parties is permitted only after prior consultation with the DKFZ Media Office (Tel. 06221 42 2854, E-mail: presse@dkfz.de). It is forbidden to use it for commercial purposes.

The German Consortium for Cancer Research (DKTK) is a joint, long-term initiative of the Federal Ministry of Education and Research (BMBF), the Federal Participating States and the German Cancer Research Center (DKFZ) and was established as one of six German Health Research Centers (DZG ). In DTCT, the German Cancer Research Center (DKFZ) is a long-term center of excellence for oncologically well-known partner sites and clinics in Germany. Research facilities and clinics in Berlin, Dresden, Essen / Düsseldorf, Frankfurt / Mainz, Freiburg, Heidelberg, Munich and Tübingen cooperate with DKFZ to create optimal conditions for clinically related cancer research. The consortium promotes interdisciplinary research topics on the interface between fundamental research and clinical practice as well as clinical studies of innovative therapeutic and diagnostic procedures. Another focus is the development of research platforms to accelerate the use of personalized cancer therapies and improve diagnosis and prevention of cancer.

More information at www.dktk.org

Press Contact:

Dr. Alexandra Moosmann
Press and Public Relations
German consortium for translational cancer research
German Cancer Research Center
In the Neuenheimer field 280
69120 Heidelberg
Phone: +49 6221 42 1662
E-mail: a.moosmann@dkfz-heidelberg.de
www.dktk.org

Dr. Sibylle Kohlstädt
Communication and Marketing
German Cancer Research Center
In the Neuenheimer field 280
69120 Heidelberg
T: +49 6221 42 2843
F: +49 (0) 6221 42 2968
E-Mail: S.Kohlstaedt@dkfz.de
E-mail: presse@dkfz.de
www.dkfz.de

Original Issues:
Raphael Brandt, Thomas Sell, Mareen Lüthen, Florian Uhlitz, Bertram Klinger, Pamela Riemer, Claudia Giesecke-Thiel, Silvia Schulze, Ismail Amr El-Shimy, Desiree Kunkel, Beatrix Fauler5, Thorsten Mielke, Norbert Mages, Bernhard G. Herrmann, Christine Sers, Nils Blüthgen & Markus Morkel: Differential activation of ERK dependent on cell type oncogeneous KRAS in colorectal carcinomas and intestinal epithelium.
Nature Communications 2019; https://doi.org/10.1038/s41467-019-10954-y

idw 2019/07