Disordered environments around tumour cells can promote cancer spread

A recent study conducted by researchers at the Institute of Science and Technology Austria (ISTA) sheds light on how tumour cells behave when exposed to a disordered microenvironment, potentially providing a biophysics model to understand how cancers spread within the human body. Led by Michael Sixt and Edouard Hannezo, the research team constructed a microfluidic chip experiment and computer simulation to demonstrate the impact of heterogeneity (disorder) surrounding a tumour on metastasis.

Cancer cells detach from the collective and invade healthy tissue, and the likelihood of detachment depends on both genetics and the local microenvironment, including blood vessels, immune cells, signalling molecules, and connective tissue. To replicate cancer cells squeezing through the pores between tissue fibres, the researchers created forests of pillars on microfluidic devices, with some forests having pillars arranged in a square lattice and others with a disordered pattern.

Fluorescence imaging and light microscopy were employed to track the behaviour of cancer cells introduced into the centre of each pillar forest. The experiments showed that tumour cell collectives were more likely to break apart in a heterogeneous environment compared to a regular geometry. The first cells detached in the disordered conditions, mirroring the detachment process observed in cancer metastasis.

To validate the experimental results, computer simulations were performed by Hannezo's group, where cells were modelled as beads moving through an environment. The simulations revealed that the beads detached from the collective more frequently in the disordered environment, suggesting a universal principle in living, or active systems. Further research by Sixt may explore the epigenetic modifications and genetic modifications that could result from cell detachment in a disordered microenvironment.