How Cancer Cells Steer Themselves Toward Optimal Environment

An international team of cell biologists has uncovered new insights into the mechanisms of cell migration and the impact of tissue rigidity on cell positioning and steering, findings that could inform efforts to stop and direct cancer cell migration.

The human body is built from billions of cells, and each cell has a specific task and carefully determined position within a tissue. Cell positioning is regulated by many factors, including tissue rigidity. Cells are capable of probing and sensing their environment, and different cell types have different preferences for optimal conditions. While this has been well-known for a long time, it has remained a mystery to researchers how cells are able to steer themselves to the optimal environment.

Let by University of Turku in Finland, an international and multidisciplinary team has uncovered how tissue stiffness determines cell positioning and regulates all types of cell migration, ranging from the neuronal growth cone turning to dissemination of malignant cancer cells in brain tumors and breast cancer.

“The prevailing view among scientists was that all cell types prefer high-rigidity environments and migrate towards increasing stiffness. This process has been coined the term ‘durotaxis’ – migration towards hard from Greek and Latin,” says Doctoral Researcher Aleksi Isomursu.“I was visiting the University of Minnesota for a research project and noticed that brain cancer cells grown on engineered substrates with alternating stiffness show the opposite behavior they turned towards soft.”

This observation launched the project, which included researchers in cancer cell biology, computational modelling and engineering and involving researchers from three continents. As the outcome, the researchers uncovered the basic mechanism all cell types use to steer themselves towards their optimal environment.

“I experimented with different types of drugs and identified ones that could make brain cancer cells stop moving or change direction,” says Postdoctoral Researcher Mathilde Mathieu.  

Identification of the mechanism of cell steering provides explanations for many thus far mysterious steps in cancer dissemination, for example how cancer cells migrate out from the stiff core of a breast tumor.

“These findings have been gaining a lot of interest in researchers and we have even played around with the idea of launching a new term – ‘mollitaxis’, migration towards soft,” says the Principal Investigator of the laboratory at the University of Turku, Professor Johanna Ivaska.

The findings were published in a recent issue of Nature Materials.