Researchers at the University of Illinois Chicago have identified a molecular switch that helps determine whether cancer cells remain soft and difficult to destroy or become stiff enough for the immune system to attack, according to a July 20 announcement. The study, led by researchers in the College of Medicine and published in the journal Developmental Cell, provides new insight into how the physical properties of cancer cells influence metastasis and points toward a potential therapeutic target.
Ekrem Emrah Er, assistant professor of physiology and biophysics and senior author of the study, said, "The physics of cancer are very counterintuitive. The outer shell of a tumor is very rigid: Even the patients can feel the hardness of a growing tumor lump. But the individual cells inside the tumor are very soft and flexible and gooey, which allows them to kind of leak out. Then they disseminate and metastasize to different organs." Er added, "If a cell is soft, it's much harder for an immune cell to attack it and shatter it. Instead, the cancer cells bend, but they don't break."
Scientists have known that metastatic cancer cells tend to be softer than healthy ones but lacked understanding about what causes this quality or how it might be targeted therapeutically. The UIC team identified an ion channel protein called KCNMB1 as playing a key role in regulating cell stiffness by controlling potassium ion movement across membranes. Activating this pathway increased cell stiffness in experiments with animal models; stiffer cancerous cells were more susceptible to attack by T cells and natural killer cells.
Alexa Gajda, first author on the paper and postdoctoral fellow at UIC, said about previous research targets, "It's not a great drug target because it's a transcription factor. If you were to mess with something that high up in a pathway, you can cause a whole bunch of downstream effects that are unintentional." Instead, Gajda explained that targeting KCNMB1 could offer practical benefits since drugs acting on ion channels already exist for other conditions.
The researchers tested BMS-204352—a potassium-channel activator—in animal models with metastatic breast cancer. Results showed reduced distant tumor growth in lungs and improved immune response against tumors when functional T cells were present.
While further research is required before clinical trials can begin in humans, Er said, "It gives us another front to fight against cancer - a biophysical front."
