Ultrasound-mediated mechanical forces activate selective tumor cell apoptosis

Area of Science:

• Biophysics
• Cell Biology
• Oncology

Background:

• Mechanical stretching induces tumor cell apoptosis and promotes normal cell growth.
• Ultrasound generates nanoscale mechanical stresses similar to those from mechanical stretching.

Purpose of the Study:

• To investigate the effect of ultrasound-mediated mechanical forces on tumor and normal cell survival.
• To elucidate the molecular mechanisms underlying ultrasound-induced tumor cell death.

Main Methods:

• Application of ultrasound to various tumor cell lines and normal cells.
• Analysis of apoptosis pathways, including mitochondrial pathways and calcium signaling.
• In vivo studies using mouse models (CT26 tumors) and chick chorioallantoic membrane (CAM) models.
• Testing on patient-derived pancreatic tumor organoids.

Main Results:

• Ultrasound induces apoptosis in tumor cells through a calpain-dependent mitochondrial pathway.
• This process relies on calcium entry via mechanosensitive Piezo1 channels.
• Tumor cell apoptosis is observed across diverse cell lines and tissues of origin, while normal cells remain unaffected.
• In vivo studies demonstrated ultrasound-mediated tumor cell killing in mouse and CAM models with minimal damage to surrounding tissues.
• Patient-derived pancreatic tumor organoids were also effectively killed by ultrasound treatment.

Conclusions:

• Ultrasound-mediated mechanical forces provide a general mechanism for inducing tumor cell apoptosis.
• The Piezo1 channel and calcium signaling are critical for this effect.
• Ultrasound represents a potential safe and non-invasive therapeutic strategy for cancer treatment augmentation.