Understanding how cancerous cells spread from a primary tumour is important for any number of reasons, including determining the aggressiveness of the disease itself.

The movement of cells into the extracellular matrix (ECM) of neighbouring tissue is an essential step in cancer progression that directly correlates to the onset of metastasis.

In APL Bioengineering, by AIP Publishing, a team of researchers from Germany and Spain used a breast cancer cell line panel and primary tumour explants from breast and cervical cancer patients to examine two different cellular contractility modes: one that generates collective tissue surface tension that keeps cell clusters compact and another, more directional, contractility that enables cells to pull themselves into the ECM.

“We focused on two parameters, namely the ability of the cells to pull on the ECM fibres and generate traction forces and on their ability to pull on each other, thereby generating a high tissue surface tension,” said author Eliane Blauth. “We linked each property to different contractile mechanisms and asked how they are connected to cancer cell escape and tumour aggressiveness.”

The team found that more aggressive cells pull more strongly on the ECM than on themselves while non-invasive cells pull more strongly on themselves than on the ECM – and that the different pulling behaviours are attributed to different structures of actin cytoskeleton inside the cells. Invasive cells use predominantly actin stress fibres — thick actin bundles that span the cell — to generate forces on their surroundings, while non-invasive cells generate forces through their actin cortex, a thin network directly under the cell membrane.

The study showed it is not the overall magnitude of these contractility modes but the interplay between them that determines a cell’s potential for escape. Experiments with only moderately invasive cells demonstrated the total force these cells generate on the ECM fibres is comparable to that of non-invasive cells, yet they can still detach and invade the ECM, which is not possible for non-invasive cells.

“The non-invasive cells still have a high cortical contractility, keeping them together, while the moderately invasive cells have a nearly disappearing cortical contractility,” said Blauth. “So not much is holding them back even though they pull much weaker on the ECM fibres.”

The team’s measurements with patient-derived vital tumour explants confirmed their findings from the cell line experiments. Here, the number of cells with a high cortical contractility decreased during tumour progression.

“This further indicates that the ability of the cells to pull on each other and hold themselves clustered together becomes weaker as the tumour grows, potentially increasing metastasis risk.”

Source: American Institute of Physics