Study provides hope for new therapies for pulmonary fibrosis and cancer

In collaboration with researchers from FAU, a team of US scientists has identified a mechanism that seems to play a significant role in both diseases

A current study could lead to completely new approaches to treatment for diseases such as pulmonary fibrosis and cancer in the medium term. Its results show that a mechanism called durotaxis plays a significant role in the progression of both diseases. Durotaxis is the migration of cells toward stiffer regions of surrounding tissue. This process contributes to the formation of scar tissue in pulmonary fibrosis and also to metastasis in some tumors. If durotaxis is prevented by an active substance, the diseases progress less severely. The study, led by Harvard Medical School in the US, also involved Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU). The results have been published in the journal Nature Cell Biology* and a commentary of the findings has been published in Cell Biology International**.

It has been known for some decades that many cells can measure the elasticity of their environment. Cells use this ability to orient themselves, for example, by migrating toward areas of tissue that are stiffer. The scientific term for this process is durotaxis, derived from the Latin durus (hard) and Greek taxis (orientation). Researchers are only beginning to understand how cells manage to do this and, above all, why.

Cells use molecular “fingers” called integrins on their outer surface to attach themselves to their surroundings (known as the extracellular space), Integrins transmit information about elasticity into the cell, where this leads to the formation of what is known as the focal adhesion complex. This complex mechanism, made up of dozens of different molecules, determines how the cell behaves in response to the stiffness of the surrounding tissue.

Targeted suppression of elasticity system

Paxillin and focal adhesion kinase (FAK) are key components in this mechanism. When they interact, they cause cell migration. “We have now suppressed the interaction between these molecules and observed the effects,” explains Prof. Wolfgang Goldmann (PhD) from the Biophysics Group at FAU.

The researchers used mice suffering from pulmonary fibrosis, which is a condition where the lungs become scarred over time and is caused, for example, by chronic inflammation. This makes the lungs less and less flexible and thus causes gradual decrease in inflation. Scar tissue also restricts gas exchange between the pulmonary alveoli and the blood. The disease can therefore be fatal.

Scar-forming cells move towards scar tissue

“We were able to demonstrate that a high stiffness gradient exists in lung tissue,” says Goldmann. “Areas that are already scarred are very stiff, whereas healthy tissue is very elastic. This gradient means that scar-forming cells, known as fibroblasts can migrate to the scarred areas making the situation worse.”

In contrast, fibroblast migration was not evident in mice where the interaction between paxillin and FAK had been deactivated using genetic modifications. Disease progression in these animals was therefore significantly milder. In addition, there is also an active substance that prevents this interaction. It also led to significantly milder symptoms in the animals without any undesired side effects.

Active substance reduces metastasis in tumors in the pancreas

“We saw similar positive effects for pancreatic cancer,” emphasizes Goldmann. Tumors in pancreatic cancer isolate themselves from the surrounding tissue with a layer of scarred cells. This makes it difficult for immune cells to penetrate the tumor and combat it. At the same time, pancreatic cancer is extremely aggressive and easily forms metastases in other areas of the body.

“We were able to show that cancer cells migrate from the soft center of the tumor to the hardened edges using durotaxis,” explains Goldmann. “They subsequently move into the surrounding tissue and migrate into the bloodstream. This is how they spread.” When durotaxis was prevented by disrupting the paxillin-FAX system, aggressive metastasis formation did not occur in the mice. Significant side effects were also not seen in this case.

“This work shows that durotaxis plays a major role in various diseases,” emphasizes Goldmann. “It is therefore a completely new approach for therapy.” Active substances that target this mechanism (and cell migration) could therefore become an important new weapon in the fight against cancer or fibrosis of the lung, heart or kidneys.

*https://doi.org/10.1038/s41556-025-01697-8

**https://doi.org/10.1002/cbin.12156

Further information:

Prof. Wolfgang H. Goldmann, PhD
Phone +49 9131 85 25605
wolfgang.goldmann@fau.de
https://bio.physik.fau.de