Cytoplasmic Viscosity is a Potential Biomarker for Metastatic Breast Cancer Cells

Abstract

Cellular microrheology has shown that cancer cells with high metastatic potential are softer compared to non-tumorigenic normal cells. These findings rely on measuring the apparent Young modulus of whole cells using primarily atomic force microscopy. This study aims to ex-plore whether alternative mechanical parameters have discriminating features with regard to metastatic potential. Magnetic rotational spectroscopy (MRS) is employed in the examination of mammary epithelial cell lines: MCF-7 and MDA-MB-231, representing low and high meta-static potential, alongside normal-like MCF-10A cells. MRS utilizes active micron-sized mag-netic wires in a rotating magnetic field to measure the viscosity and elastic modulus of the cy-toplasm. All three cell lines display viscoelastic behavior, with cytoplasmic viscosities ranging from 10-70 Pa s and elastic moduli from 30-80 Pa. It is found that the tumorigenic MCF-7 and MDA-MB-231 cells are softer than the MCF-10A cells, with a twofold decrease in elastic modu-lus. To differentiate cells with low and high malignancy however, viscosity emerges as the more discriminating parameter, as MCF-7 exhibits a 5 times higher viscosity as compared to MDA-MB-231. These findings highlight the sensitivity of cytoplasmic viscosity to metastatic potential, suggesting its potential utility as a mechanical marker for malignant cancer cells.

Cell viscosity influences hematogenous dissemination and metastatic extravasation of tumor cells

“…It is tempting to suggest that probing the molecular (EMT status) and the mechanical profiles (elasticity and viscosity) of patient-derived tumor cells, especially CTCs, is likely to provide useful prognostic markers. Interestingly and in line with our observations, recent evidence suggest that viscosity might be a strong indicator of the metastatic potential of tumor cells (Dessard et al, 2024). This once again begs the question of whether tumor cells might also dynamically adjust their mechanical properties based on their environment in order to progress along their metastatic journey.…”

“…This was not the case for elasticity, reinforcing the need to dissect which cellular components control one (viscosity) or the other (elasticity). Interestingly, recent evidence suggests that cytoplasmic viscosity bears potential in as a mechanical marker for metastatic tumor cells (Dessard et al, 2024). Yet, one cannot fully exclude a lesser contribution of elasticity in the process of CTCs seeding capillary-sized vessels, as we also found low elasticity to facilitate elastic bead entry in small vessels.…”