▷ Predict whether a tumor can metastasize

14.07.2021 – 08:00

Swiss National Science Foundation / Swiss National Fund

Bern (ots)

In cancer, the cells that break out and metastasize are particularly dangerous. A research team supported by the Swiss National Science Foundation has found a method to identify such cells.

Cancer treatments are sometimes made difficult by the many different cells in a tumor. It would be important to be able to target the cells that can trigger metastases. A team supported by the Swiss National Science Foundation (SNSF) has now been able to show how metastases develop and which cells are responsible for them.

The researchers have succeeded in identifying and characterizing the most dangerous cells in Ewing’s sarcoma. This cancer is a very aggressive bone cancer with a high potential for metastasis, which affects mainly children and young adults. Among the very active genes in these cells, the research team found a gene that is known to correlate with a poor prognosis. When this gene is active, the likelihood that the cancer cells will spread in the body and form metastases increases, the researchers explain. The results of this work were published in the journal Science Advances

released.

These results are a first step towards developing more targeted treatments, says Ivan Stamenkovic, Professor of Experimental Pathology at the University Hospital Lausanne (CHUV) and co-author of the publication with Nicolo Riggi, Assistant Professor at the CHUV. “The identification of the gene that correlates with a higher risk of metastasis opens up new avenues for research: It should be possible to target the protein encoded by this gene with the treatment and to eliminate these particularly aggressive cells,” explains the scientist.

Dangerous glow

In a first step, the researchers had to isolate the cells that form metastases. To do this, they took tumors from those affected and cultivated them under conditions similar to those found in the human body. In this way, they were able to produce tumor models, so-called organoids. This method enabled the researchers to genetically modify the cells by adding a gene that produces a green fluorescent protein. This gene has also been modified so that it can be suppressed by a very short, special RNA molecule (a micro-RNA) that is produced by the cells themselves. Since the metastatic cells produce little of this micro-RNA, the production of the fluorescent protein is not suppressed. Hence, they glow and so can be easily identified. “It should be possible to use this tool on other types of tumors in order to better understand aggressive cells,” says Nicolo Riggi.

T. Keskin, B. Rucci, S. Cornaz-Buros, P. Martin, C. Fusco, L. Broye, K. Cisarova, I. Letovanec, S. La Rosa, S. Cherix, M. Diezi, R. Renella, P. Provero, I. Stamenkovic und N. Riggi: A live single-cell state reporter assay links intra-tumor heterogeneity to metastatic proclivity in Ewing sarcoma, Science Advances (2021).

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Cancer cells are more tolerant

In his research project, Ivan Stamenkovic is particularly interested in the mechanisms that are responsible for the onset and development of cancer. “In the majority of cancers, the metastatic cells have certain properties of stem cells,” explains the researcher. “This distinguishes them from other cells that make up the bulk of the tumor. Since these cells play an important role in the regeneration of tissue, they must have a high degree of flexibility. Therefore, they are more tolerant when an event such as a genetic mutation occurs and are more likely to transform into a cancer cell. Their protective mechanisms are partially or completely suppressed. ”

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Support for research in all disciplines

This work has benefited from project funding from the SNSF. After a selection process, scientists can independently carry out a research project on topics and research goals of their own choosing.

Project funding

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The text of this media release and further information are available on the website of the Swiss National Science Foundation.

Press contact:

Ivan Stamenkovic, CHUV, University Institute of Pathology, Rue du Bugnon 25, 1011 Lausanne, Tel: +41 79 556 79 95, E-Mail: [email protected]

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