New clue discovered for how and why cancer cells spread

An international team of researchers has uncovered a new mechanism that enables cancer cells to move throughout the body, providing a potential new target to stop metastasis, which is responsible for 90 per cent of cancer deaths.

In findings published in Nature, the team identifies that cancer cells move faster when they are surrounded by thicker fluids, a change that occurs when lymph drainage is compromised by a primary tumour.

"This is really the first time that the viscosity of the extracellular fluid has been looked at in detail," says John D. Lewis, professor and Bird Dogs Chair in Translational Oncology at the University of Alberta's Faculty of Medicine & Dentistry. "Now that we know that fluid viscosity signals cancer cells to move in a specific way, we can potentially use drugs to basically short-circuit that signalling pathway and encourage cancer cells to slow down, or even maybe to stop."

The Lewis lab was invited to join the project led by researchers at Johns Hopkins University, because of its expertise in imaging human cancer cells in real-time motion using the placenta-like chorioallantoic membrane from fertilized chicken eggs.

"I would say we're the world leaders in this type of imaging," Lewis says. "Our contribution to the work was to very precisely show that cancer cells change their gene expression when they encounter increased viscosity in the surrounding fluid and become more aggressive. And even when you bring the viscosity back down, these cells stay more aggressive."

"We then went on to show that when this signalling pathway is perturbed in cancer cells it changes their ability to escape the bloodstream and metastasize," Lewis says.

This is the third paper the international research team has published. Lewis credits Konstantin Stoletov, senior research associate, for the bulk of his team's work. He cautions that once a new therapeutic target is identified, it could take 10 to 15 years to develop and test a drug.

Bera K, Kiepas A, Godet I, et al.
Extracellular fluid viscosity enhances cell migration and cancer dissemination.
Nature 611, 365-373, 2022. doi: 10.1038/s41586-022-05394-6

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