Tumor physics: Cancer cells liquefy and squeeze through the tissue

Scientists from the University of Leipzig, in collaboration with colleagues from Germany and the USA, have made a breakthrough in research into the spread of cancer cells. The biophysicists around Prof. Dr. In experiments, Josef Alfons Käs, Steffen Grosser and Jürgen Lippoldt were able to demonstrate for the first time how cells deform in order to move in dense tumor tissue and squeeze through their neighboring cells. The researchers found that motile cells work together to liquefy the tumor tissue.

Käs carried out the research project in cooperation with Prof. Dr. Lisa Manning from the University of Syracuse (USA) and Prof. Dr. Bahriye Aktas from the Leipzig University Hospital. They have now published their results in "Physical Review X", a leading specialist journal for physics, which mainly publishes groundbreaking research results.

"These first observations of a phase transition in human tumors change our basic concepts of tumor progression and could improve cancer diagnosis and therapy," says Käs, who has been studying the physical properties of cancer cells for years. The research has shown that human tumors contain solid and liquid cell clusters, representing a breakthrough in understanding tumor mechanics. The results formed the basis for the first method that can be used to detect metastasizing cancer cells in the tumour.

In tumor samples from patients at the university clinic, the scientists found regions with mobile cells as well as stable, solid-like regions without cell movement. From a physical point of view, cells should not be able to move in the dense tumor mass - tumors are so densely crowded with cells that in any classical material the movement would be arrested.

The researchers therefore developed a new approach in the live microscopy of tumors by staining human tumor samples fluorescently immediately after the operation and thus being able to observe cell movements live. They found out that, contrary to all previous knowledge, this cell movement does take place and is associated with strong nuclear deformations. They observed cells and their nuclei literally squeezing through the tissue by deforming greatly.

“Cells in biological tissues behave in a similar way to people in a bar. At low densities, they can move freely. However, when it is very crowded, any movement becomes difficult. But even in a crowded bar, you can still push your way through if you turn sideways. We see exactly this effect in tumor tissue,” explains Käs. The researchers believe this fluid transition explains how cells in a tumor can move and multiply, eventually leading to metastasis. The fluid tissues were enriched with elongated, deformed cells and nuclei. Static images of elongated cell and nuclear shapes could thus serve as a fingerprint for the metastatic aggressiveness of a tumor.

“These are spectacular results from the field of cancer physics. We now need to investigate whether the fluid regions can predict tumor aggressiveness. Here we found a cancer marker that indicates active, mobile regions and that is based on a simple physical mechanism," says Steffen Grosser. Professor Käs is currently initiating a clinical study to investigate the potential of the cell and nuclear form as a new tumor marker that could be used to examine and treat patients in a much more targeted manner than previously.

Original title of publication in Physical Review X:
Cell and Nucleus Shape as an Indicator of Tissue Fluidity in Carcinoma
DOI: doi.org/10.1103/PhysRevX.11.011033

Further information:
Prof. Dr. Josef A. Kas
Peter Debye Institute for Soft Matter Physics at the University of Leipzig
Telefon: + 49 341 97-32470
Email: jkaes@physik.uni-leipzig.de
Web: http://www.uni-leipzig.de/~physik/exp1.html

Steffen Grosser
Peter Debye Institute for Soft Matter Physics at the University of Leipzig
Mobilephone: + 49 341 97 32562
Email: steffen.grosser@uni-leipzig.de

Source: Press release University of Leipzig from April 18.02.2021th, XNUMX