Universität Leipzig: Researchers are developing a new marker for the motility of cancer cells

Scientists led by the University of Leipzig have found a groundbreaking application of the scientific field of "Physics of Cancer" in oncology. This marks a milestone for the new scientific field, demonstrating for the first time their applicability in medicine. Based on tissue and cell mechanics and the use of machine learning, they have developed a marker for the mobility (motility) of cancer cells in digital pathology. The new information about breast tumors provided by the marker improves the prediction of the risk of developing metastases even after a decade. The researchers have just published their new findings in the renowned journal Physical Review X.

In a retrospective study of 1.380 breast cancer patients carried out in close collaboration with Prof. Dr. Axel Niendorf from the Hamburg-West pathology department, the doctoral student Pablo Gottheil from the working group of Prof. Dr. Josef Alfons Käs from the University of Leipzig found that a joint transition of the cancer cells to mobility, known among experts as "unjamming", significantly increases the risk of distant metastases. Distant metastases occur when the cancer cells invade other organs. "This process plays a crucial role in cancer aggressiveness and could be an important additional prognostic factor for the risk of a tumor spreading," says Prof. Dr. Josef Alfons Käs, Head of the Department of Soft Matter Physics at the University of Leipzig.

In the primary tumor, the cancer cells form clusters in which they are so tightly packed that they "jam" one another and cannot move. In the course of tumor growth, there is a collective mobility transition, which allows the cancer cells to leave the tumor and spread. The cancer cells take on an elongated shape that enables them to push past one another. The histological tumor sections used in the diagnosis of breast cancer are static images in which cell movement cannot be followed. "Now we have realized that we can identify mobile cancer cells in these histological images based on their elongated shape and lower density. We have therefore developed a first marker that makes it possible to detect motile cancer cells, which can spread and therefore spread, in histological tumor sections. We were able to show that a large number of such motile cells in a tumor sample significantly increases the risk of metastasis,” explains biophysicist Käs.

Less over- and under-treating of patients

“Breast cancer therapies could be significantly improved if more precise diagnostics were possible. There are many different, differentiated treatment approaches. However, since the current diagnostics cannot predict exactly how the disease can progress, the patients are over- and under-treated,” explains Käs. An essential aspect of the prognosis is to predict whether metastases will form in the body. Affected lymph nodes in the armpit pose a high risk. However, around 30 percent of women with affected lymph nodes do not develop distant metastases, while the tumor can spread throughout the body in 30 percent of women without affected lymph nodes.

According to the underlying study, the new prognostic marker developed by Käs and his colleagues has a clinically relevant predictive power that is comparable to the lymph node status previously used in diagnostics. The two diagnostic criteria are complementary in their predictive power and thus correct each other's mispredictions. As a result, there is a possibility that fewer women will be over- or under-treated. Above all, the new marker allows an earlier prognosis, since it can already make a prediction before the cancer cells have left the tumor. This means that a prognosis can also be given for patients at an early stage of the disease, for whom the lymph node status is not yet effective. The researchers' new approach could therefore be particularly relevant for the early identification of particularly aggressive tumors.

Procedure also applicable to other tumor types

These results could only be obtained through close cooperation with physicians. According to Käs, the study could not have been carried out without the large number of digital histological sections of breast tumors provided by Prof. Niendorf. The clinic for gynecology at the University Hospital Leipzig under the direction of Prof. Dr. Bahriye Aktas provided vital breast tumor explants. The biophysicists were thus able to confirm that the morphological "unjamming" criteria actually apply to motile cancer cells. Prof. Dr. Markus Löffler from the Institute for Medical Informatics, Statistics and Epidemiology at the University of Leipzig and his team supported the project with clinical evaluation and interpretation.

“I am very happy about these exciting results. With the evaluation of unjamming, we will have another prognostic marker at our disposal in the future, which can usefully supplement our current diagnostic spectrum. However, before the marker can find its way into clinical practice, further prospective studies are necessary,” emphasizes Prof. Dr. Bahriye Aktas. Since the method does not rely on specific molecules in the tumor, it could also be applied to other tumor types. According to the researchers, it is therefore possible to use the procedure in 92 percent of all cancer patients. In addition, unjamming can be an important pathological factor in other diseases, such as asthma.

With more than two million cases worldwide every year, breast cancer is by far the most common cancer in women. More than 2018 women with breast cancer died in 600.000, largely due to the systemic, invasive nature of the disease.

Original title of publication in “Physical Review X”:
Pablo Gottheil, Jürgen Lippoldt, Steffen Grosser, Frédéric Renner, Mohamad Saibah, Dimitrij Tschodu, Anne-Kathrin Poßögel, Anne-Sophie Wegscheider, Bernhard Ulm, Kay Friedrichs, Christoph Lindner, Christoph Engel, Markus Löffler, Benjamin Wolf, Michael Höckel, Bahriye Aktas, Hans Kubitschke, Axel Niendorf, and Josef A. Käs: "State of Cell Unjamming Correlates with Distant Metastasis in Cancer Patients", DOI: 10.1103/PhysRevX.13.031003

Source: Press release from the University of Leipzig from July 11.07.2023st, XNUMX