Mar 04: The continuous movement of the vocal cords weakens and eventually stops as laryngeal cancer progresses. Researchers have, for the first time, discovered that restoring cellular vibration reduces the aggressiveness of advanced vocal cord cancer. When cancer cells were exposed to sound-wave vibration, a protein that promotes cancer growth and severity decreased.
“What music should we play to our cells?” This question sparked a groundbreaking study on laryngeal cancer that revealed a previously unknown sensitivity of this cancer type to a targeted drug currently under development.
Laryngeal cancer is one of the most common malignant tumours of the head and neck region. The most common early symptom is hoarseness, as the cancer typically appears in the vocal cords, and their movement gradually becomes impaired as the disease develops. Movement decreases because the vocal cord tissue stiffens and the cancer invades surrounding tissue.
The most significant risk factors are smoking and heavy alcohol consumption. The prognosis for advanced laryngeal cancer is poor, and there are currently no targeted drug therapies available.
Stiffer the tissue, more malignant the cancer
Researchers have long known that increased tissue stiffness promotes cancer malignancy in non-moving tissues such as breast, liver, and pancreatic cancers, because cells sense and respond to the physical properties of their environment. The sensitivity of cells to external forces led researchers to take an interest in laryngeal cancer, which develops in constantly moving tissue.
“We wondered whether ‘movement could be medicine’ and whether tissue stiffening and immobilisation contribute to cancer development,” says Academy Professor Johanna Ivaska, Director of the BarrierForce Centre of Excellence funded by the Research Council of Finland.
“We developed this idea together with BarrierForce Vice Director Professor Sara Wickström and her research group. With their help, we used a bioreactor in which cells were grown on a vibrating membrane placed on top of a loudspeaker,” explains Ivaska.
The study included researchers from the BarrierForce Centre of Excellence and the InFLAMES Research Flagship. The study’s lead author, Jasmin Kaivola, who recently completed her doctoral degree at the University of Turku in Finland, came up with the idea of connecting an old mobile phone to the device to play sounds and music, and the experiments began.
Vibration affected cancer cells
The researchers’ predictions proved correct: exposing cancer cells to vibration-mimicking vocal cord movement reduced their malignancy. One of the observed changes was a decrease in a protein called YAP in the cells.
Using samples of early-stage and advanced laryngeal cancer collected from approximately 200 Finnish patients, the researchers found that elevated expression of proteins that increase tissue stiffness enhanced YAP activity and predicted mortality. In an experimental cancer model, the researchers discovered that the cancer was sensitive to a targeted drug under development that inhibits YAP protein activity.
Jasmin Kaivola notes that the study is entirely groundbreaking because the biomechanics of developing cancers have not previously been studied in moving tissues. She says it would be interesting to investigate whether the mechanism they identified has prognostic value in other cancers of moving tissues, such as lung cancer.
“We are excited about the results and believe that our findings may encourage developers of these drugs to explore their suitability for this difficult-to-treat cancer with a poor prognosis,” says Kaivola.
The study was recently published in the highly prestigious scientific journal Nature Materials. The project, conducted primarily in the research laboratory of Academy Professor Johanna Ivaska at the Turku Bioscience Centre in Finland also involved three clinicians treating and studying oral cancers at the University Hospitals of Turku and Helsinki, as well as soft matter physicists from the University of Vienna and Milan.
InFLAMES is a joint flagship initiative of the University of Turku and Åbo Akademi University. Its aim is to identify new drug development targets and promote drug development in collaboration with biotechnology and pharmaceutical companies. The flagship also advances diagnostics to enable tailored targeted therapies for patients. InFLAMES is part of the Academy of Finland’s Flagship Programme.
