An international research team has discovered a potential new target for a drug that could prevent the deadly metastases responsible for 90% of cancer deaths.
According to a study published in Nature, an international team of researchers has identified a mechanism that allows cancer cells to spread throughout the body. They found that cancer cells move faster when they are surrounded by thicker fluids, a change that occurs when lymph drainage is disrupted by a primary tumor.
These findings provide a potential new target for stopping metastasis, which is responsible for 90% of cancer deaths.
“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 signaling 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 signaling 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.
Reference: “Extracellular fluid viscosity enhances cell migration and cancer dissemination” by Kaustav Bera, Alexander Kiepas, Inês Godet, Yizeng Li, Pranav Mehta, Brent Ifemembi, Colin D. Paul, Anindya Sen, Selma A. Serra, Konstantin Stoletov, Jiaxiang Tao, Gabriel Shatkin, Se Jong Lee, Yuqi Zhang, Adrianna Boen, Panagiotis Mistriotis, Daniele M. Gilkes, John D. Lewis, Chen-Ming Fan, Andrew P. Feinberg, Miguel A. Valverde, Sean X. Sun and Konstantinos Konstantopoulos, 2 November 2022, Nature.