Self organisation of invasive breast cancer driven by the interplay of active and passive nematic dynamics

TL;DR

This study uncovers that invasive breast cancer cell clusters self-organize through active nematic dynamics driven by cell motility, influencing tumor progression and patient prognosis.

Contribution

It demonstrates that cancer cell clustering results from active self-organization involving nematic dynamics, combining simulations and histological analysis to reveal new mechanisms.

Findings

Motile cancer cells form active nematic aggregates within aligned ECM fibers.

Cluster activity correlates with tumor progression and prognosis.

Scaling behaviors of clusters reflect underlying active nematic dynamics.

Abstract

In invasive breast cancer, cell clusters of varying sizes and shapes are embedded in the fibrous extracellular matrix (ECM). Although the prevailing view attributes this structure to increasing disorder resulting from loss of function and dedifferentiation, our findings reveal that it arises through a process of active self-organization driven by cancer cell motility. Simulations and histological analyses of tumours from over 2,000 breast cancer patients reveal that motile, aligned cancer cells within clusters move as active nematic aggregates through the surrounding highly aligned ECM fibres, which form a confining, passive nematic phase. Cellular motion leads to cluster splitting and coalescence. The degree of cluster activity, combined with heterogeneity in cell motility, is reflected in specific scaling behaviours for cluster shape, size distribution, and the distance between cluster boundaries and nematic defects in ECM alignment. Increased activity estimates correlate with tumour progression and are associated with a poorer prognosis for patients.