A 'Spicy' Mechanotransduction Switch: Capsaicin-Activated TRPV1 Receptor Modulates Osteosarcoma Cell Behavior and...

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Mechanobiology

Background:

• Osteosarcoma (OS) is a primary bone cancer characterized by heterogeneity and treatment resistance.
• The role of mechanical forces in OS progression is not well understood.
• Molecular drivers of OS are known, but mechanical stimuli's impact remains underexplored.

Purpose of the Study:

• To investigate the role of the transient receptor potential vanilloid 1 (TRPV1) channel in osteosarcoma mechanotransduction.
• To determine if TRPV1 activation influences OS cell metastatic traits and drug responsiveness.
• To explore TRPV1 as a potential therapeutic target in aggressive OS.

Main Methods:

• Uniaxial cyclic stretch applied to OS cell lines (U-2 OS, SAOS-2).
• Confocal microscopy, immunohistochemistry, and atomic force microscopy.
• Treatment with capsaicin (TRPV1 agonist) and chemotherapeutic agents (doxorubicin, cisplatin).

Main Results:

• Aggressive U-2 OS cells showed TRPV1-dependent reorientation under mechanical stretch, unlike SAOS-2 cells.
• Capsaicin mimicked mechanical effects, altering OS cell adhesion, migration, and drug sensitivity.
• TRPV1 activation differentially regulated Src and acetylated histone H3 (acH3) levels, impacting the Src-acH3 mechanosignaling axis.
• Effects were tumor-specific and absent in healthy osteoblasts.

Conclusions:

• TRPV1 acts as a key regulator of mechanotransduction in osteosarcoma.
• TRPV1 activation integrates mechanical and chemical cues, driving epigenetic remodeling and phenotypic plasticity in OS.
• TRPV1 is a promising therapeutic target for aggressive, drug-resistant osteosarcoma subtypes.