Investigating cell death responses associated with histotripsy ablation of canine osteosarcoma

Area of Science:

• Oncology
• Biotechnology
• Veterinary Medicine

Background:

• Osteosarcoma (OS) is a common primary bone tumor in dogs and humans, necessitating novel therapeutic strategies.
• Histotripsy is an emerging tumor ablation technique requiring evaluation of residual tumor cell behavior post-treatment.
• Understanding the fate of non-ablated OS cells is crucial for clinical histotripsy translation.

Purpose of the Study:

• To characterize the cell death genetic signature and proliferation response of canine OS cells after near-complete histotripsy ablation.
• To evaluate the in vivo genetic cell death signatures associated with histotripsy ablation in canine OS tumors.

Main Methods:

• Canine OS cell lines were ablated using histotripsy to achieve near-complete tumor destruction.
• The genetic cell death signature of remaining viable OS cells (4%) was analyzed in vitro.
• In vivo canine OS tumors were ablated, and genetic cell death signatures were assessed 24 hours post-ablation.

Main Results:

• Differential gene expression in viable OS cells and ablated tumors indicated pathways associated with immunogenic cell death (ICD).
• Remaining viable canine OS cells exhibited significantly reduced proliferation compared to control cells in vitro.
• Genetic markers for ICD were observed in both in vitro and in vivo samples.

Conclusions:

• Histotripsy ablation of canine OS induces cell death, potentially through both direct and indirect mechanisms.
• Reduced proliferation in residual OS cells and ICD signatures suggest a favorable post-ablation cellular response.
• Findings support histotripsy as a promising modality for osteosarcoma treatment, with implications for both veterinary and human medicine.