IISc study: Tweaking cell spacing enhances cancer treatment with ultrasound

Bengaluru: A new study by the Department of Bioengineering (BE) at the Indian Institute of Science (IISc), in collaboration with other researchers, has found that adjusting the spacing between cancer cells can make them more susceptible to ultrasound treatment.

The extracellular matrix (ECM) — a network of macromolecules and minerals —provides structural and biochemical support to surrounding cells. Cells have surface receptors called integrins that bind to repetitive spacings on the ECM, aiding their growth and spread.

Ultrasound waves at 39 kHz can disrupt the cancer cell membrane, triggering cell death through a relatively low-cost and non-invasive approach. "Unlike normal cells, cancer cells lack repair mechanisms to withstand the mechanical forces exerted by ultrasound waves," the researchers stated in a press release on Monday.

"In normal tissue, ECM spacing is around 50-70 nanometres (nm), but in the tumour microenvironment, excessive ECM secretion causes severe choking, reducing the binding spacing to below 50 nm. We found that increasing the binding spacing to around 50-70 nm led to higher cancer cell death,” explained Prof Ajay Tijore, corresponding author of the study.

When ultrasound was applied to cancer cells with 50 nm and 70 nm spacings, their membranes stretched due to forces exerted by a filament protein called myosin, ultimately triggering cell death.

During their experiments, the team came across literature on Cilengitide, a drug that blocks integrin-ECM binding. “We tested what happens when a very low dose of Cilengitide — about 1,000 times lower than in previous trials — is combined with ultrasound treatment," said S Manasa Veena, PhD student and first author of the study.

“The drug tricks cancer cells into perceiving a change in spacing, causing them to develop myosin forces, which then trigger cell death,” added Tijore.

The research team has partnered with clinicians to test this combination therapy on oral cancer tissue samples, as oral cancer remains a major health concern in the Indian subcontinent.