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Ultrasound Mechanostimulation Shows Promise In Selectively Targeting Oral Cancer Cells

Rashmita Luha (left) and Ajay Tijore (right) (Credit: Siddhesh Saigaonkar)

New study suggests low-frequency ultrasound-induced mechanical stimulation can selectively kill oral cancer cells while largely sparing healthy cells.

Researchers at the Indian Institute of Science (IISc), working with clinicians at MS Ramaiah Medical College and Hospitals, have demonstrated that low-frequency ultrasound-induced mechanical stimulation can selectively kill oral cancer cells while largely sparing healthy cells, offering a potential new direction for treating one of India’s most prevalent cancers.

Oral cancer remains a major public health challenge in India, driven largely by widespread tobacco and areca nut consumption. Although surgery, chemotherapy and radiotherapy have improved outcomes, these treatments often damage healthy tissues alongside tumours, leading to significant side effects and affecting patients’ quality of life.

In the study, the researchers investigated whether moderate mechanical forces generated by low-frequency ultrasound could exploit a unique weakness in oral cancer cells. Instead of relying on conventional laboratory cell lines, the team used patient-derived oral tumour samples, enabling them to capture biological variations that better reflect Indian patients.

The researchers found that oral cancer cells are particularly susceptible to ultrasound-generated mechanical stimulation. The vulnerability appears to be linked to reduced levels of Tropomyosin 2.1, a mechanosensory protein that enables cells to sense and withstand physiologically relevant mechanical forces. When exposed to ultrasound, cancer cells underwent selective cell death, whereas healthy oral epithelial cells remained largely unaffected.

“The novelty of this study lies in showing how ultrasound mechanostimulation can selectively target oral cancer cells by exploiting their mechanical weakness,” says Ajay Tijore, Assistant Professor at the Department of Bioengineering, IISc, and corresponding author. “Instead of using heat or drugs, this approach uses moderate mechanical forces to damage cancer cells beyond their ability to recover.”

Beyond inducing cell death, the researchers observed that ultrasound substantially reduced the ability of oral cancer cells to migrate and invade surrounding tissues, two key processes involved in cancer progression.

Using a three-dimensional co-culture platform designed to mimic the oral tumour microenvironment, the team also found that ultrasound disrupted the dense capsule-like barrier formed by cancer-associated cells around the tumour. Such barriers are known to impede the penetration of drugs and immune cells into tumours, limiting the effectiveness of existing therapies.

“What surprised us most was the consistency of the response across cancer cells derived from multiple patients from different cancer stages. They were highly vulnerable to ultrasound, while normal cells were much less affected,” says Rashmita Luha, PhD student in the Department of Bioengineering and first author.

The researchers say the findings are encouraging because ultrasound is already widely used in clinical practice and is a non-invasive technology. They suggest that ultrasound mechanostimulation could eventually provide a safer and more targeted approach for treating oral cancer by exploiting the mechanical weakness of cancer cells.

However, they caution that the work is at a preclinical stage and requires validation in more advanced disease models before it can be translated into clinical applications. If confirmed, the approach could also have potential in other accessible solid tumours, including breast and skin cancers.

“The clinical collaboration was very important because it allowed us to work with patient-derived oral tumour samples rather than relying only on standard cell lines developed in Western countries,” says Tijore. “In the future, we want to test this approach in more physiologically relevant models and explore whether ultrasound can be combined with existing treatments to improve drug penetration and therapeutic outcomes.”

Disclaimer:
SciSoup declares no competing interests. This article is based on a press release from the Indian Institute of Science (IISc) and has been independently edited for clarity, accuracy, and readability.

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