Mechanical compression regulates tumor spheroid invasion into a 3D collagen matrix

TL;DR

This study investigates how mechanical compression influences tumor spheroid invasion into a 3D collagen matrix, revealing differential responses between malignant and non-tumorigenic cells, with implications for tumor mechanics and invasion.

Contribution

It introduces a modified Transwell assay to apply constant compression and compares the invasion behaviors of malignant and non-tumorigenic spheroids under compression.

Findings

Malignant spheroids increase motility and invasion under compression.

Non-tumorigenic spheroids decrease motility and do not detach under compression.

Compression affects tumor and healthy tissues differently, impacting invasion dynamics.

Abstract

Uncontrolled growth of tumor cells in confined spaces leads to the accumulation of compressive stress within the tumor. Although the effects of tension within 3D extracellular matrices on tumor growth and invasion are well established, the role of compression in tumor mechanics and invasion is largely unexplored. In this study, we modified a Transwell assay such that it provides constant compressive loads to spheroids embedded within a collagen matrix. We used microscopic imaging to follow the single cell dynamics of the cells within the spheroids, as well as invasion into the 3D extracellular matrices (EMCs). Our experimental results showed that malignant breast tumor (MDA-MB-231) and non-tumorigenic epithelial (MCF10A) spheroids responded differently to a constant compression. Cells within the malignant spheroids became more motile within the spheroids and invaded more into the ECM under compression; whereas cells within non-tumorigenic MCF10A spheroids became less motile within the spheroids and did not display apparent detachment from the spheroids under compression. These findings suggest that compression may play differential roles in healthy and pathogenic epithelial tissues and highlights the importance of tumor mechanics and invasion.