Cancer Cell Biomechanical Properties Accompany Tspan8-Dependent Cutaneous Melanoma Invasion

Area of Science:

• Biophysics
• Cancer Biology
• Cellular Mechanics

Background:

• The biomechanical properties of cancer cells, particularly their stiffness, are not well understood.
• Investigating cell stiffness is crucial for understanding cancer cell invasion and progression.

Purpose of the Study:

• To determine if changes in melanoma cell stiffness influence their invasive potential.
• To correlate cell stiffness with morphological and molecular changes associated with epithelial-to-mesenchymal transition (EMT).

Main Methods:

• Atomic force microscopy (AFM) was used to measure cell stiffness in vitro and in vivo.
• Experiments involved melanoma cell lines, human skin constructs, and Medaka fish models.
• Gene expression analysis was performed, including ZEB1 overexpression to induce EMT.

Main Results:

• Reduced melanoma cell stiffness correlated with increased invasiveness across different models.
• Stiffness modulation was linked to morphological changes indicative of mesenchymal characteristics.
• ZEB1-induced EMT decreased cell stiffness and promoted tetraspanin-8-mediated invasion.
• ZEB1 and Tspan8 expression correlated in human melanoma lesions.

Conclusions:

• Intrinsic cell stiffness is a significant factor in melanoma cell invasion.
• Decreased cell stiffness is associated with EMT and enhanced invasive properties in melanoma.
• Cell stiffness may serve as a relevant biomarker for human cutaneous melanoma progression.