Researchers develop new marker for the motility of cancer cells

The new information on breast tumours provided by the marker improves the prediction of the risk of metastases occurring 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, which was conducted in close collaboration with Prof. Dr Axel Niendorf from the Hamburg Department of Pathology. Axel Niendorf from the Department of Pathology Hamburg-West, doctoral student Pablo Gottheil from the working group of Prof Dr Josef Alfons Käs from the University of Leipzig found that a common transition of cancer cells to motility, known in specialist circles as „unjamming“, significantly increases the risk of distant metastases. Distant metastases occur when the cancer cells invade other organs. „This process plays a decisive role in cancer aggressiveness and could be an important additional prognostic factor for the risk of a tumour spreading,“ says Prof. Dr. Josef Alfons Käs, Head of the Department of Soft Matter Physics at the University of Leipzig.

In the primary tumour, the cancer cells form clusters in which they are densely packed so that they pinch each other („jamming“) and cannot move. As the tumour grows, a collective mobility transition occurs, allowing the cancer cells to leave the tumour and spread. In the process, the cancer cells take on an elongated shape that enables them to squeeze past each other. The histological tumour sections used in the diagnosis of breast cancer are static images in which the cell movement cannot be followed. „Now we have realised that we can identify moving 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 that can spread and therefore scatter in histological tumour sections. We were able to show that a high number of such motile cells in a tumour sample significantly increases the risk of metastasis,

explains biophysicist Käs.

Less overtreatment and undertreatment of patients
„Breast cancer therapies could be significantly improved if a more precise diagnosis were possible. There are many different, differentiated treatment approaches. However, as the current diagnosis cannot predict exactly how the disease may progress, patients are over- and under-treated," explains Käs. A key aspect of the prognosis is to predict whether metastases will form in the body. The current main criterion for assessing the risk of metastasis, i.e. the spread of the cancer, is the involvement of the lymph nodes near the tumour. However, there is still a significant margin of error in this risk prediction. Around 30 percent of women with affected lymph nodes do not develop distant metastases, while the tumour spreads 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 false predictions. This offers the possibility that fewer women will be over- or under-treated. Above all, the new marker allows an earlier prognosis, as it can make a prediction before the cancer cells have even left the tumour. This means that a prognosis can also be given for patients at an early stage of the disease in whom the lymph node status is not yet effective. The researchers' new approach could therefore be relevant for the early identification of particularly aggressive tumours.

Method also applicable to other tumour types
These results could only be obtained through close collaboration with doctors. Without the large number of digital histological sections of breast tumours provided by Prof. Niendorf, the study would not have been able to be carried out, according to Käs. The Department of Gynaecology at Leipzig University Hospital, headed by Prof. Dr Bahriye Aktas, provided vital breast tumour explants. This enabled the biophysicists to confirm that the morphological „unjamming“criteria actually apply to motile cancer cells. Prof. Dr Markus Löffler from the Institute of Medical Informatics, Statistics and Epidemiology at Leipzig University and his team supported the project with the clinical evaluation and interpretation.

Since the method does not rely on specific molecules in the tumour, it could also be used for other tumour types. According to the researchers, it is therefore possible to apply the procedure to 92 per cent of all cancer patients.

With over two million cases worldwide every year, breast cancer is by far the most common cancer in women. In 2018, more than 600,000 women with breast cancer died, mainly due to the systemic, invasive nature of the disease.