Our arsenal of weapons to fight cancer is by no means empty, but what exactly makes a cell cancerous is a question we've yet to answer. We know that malignant tissue is often measurably stiffer than healthy tissue, and that cancerous cells respond differently to their environment than healthy cells, prompting a large-scale finger-pointing at the stuff around cells — the so-called extracellular matrix. But Katarzyna Pogoda and colleagues have determined that these differences can also arise from the way cells respond to pressure gradients within a tissue, which are particularly large in brain tumours (New J. Phys 16, 075002; 2014).

Credit: © BSIP SA / ALAMY

Variation in the mechanical response of healthy and malignant tissue is usually measured by changes in shear storage or the Young's modulus of a sample. Common wisdom currently links these changes to increases in the production and composition of the protein-rich extracellular matrix. Some even go as far as saying that it's essential to the elevated stiffness observed in tumour cells. But oddly, the extracellular matrix is all but absent in our brains. Tumours, on the other hand, are not.

It turns out that much of what we know about the rheology of brain tissue varies wildly across studies using different methods and model systems. Responding to this variation, Pogoda et al. set out to measure the relative stiffness of malignant and healthy brain tissue — and what they found was intriguing.

When both types of cell were isolated in vitro, they responded to increased substrate stiffness by spreading out and stiffening, just as one would expect of cells taken from other parts of the body. But when the authors looked at tissue samples large enough to be viewed by the naked eye, and subjected them to low levels of strain, they found that the malignant brain was not stiffer than its healthy counterpart — in stark contrast to similar results for breast cancer, for example. Even more telling, was the fact that the shear moduli of both tissue types increased dramatically under uniaxial compression.

The mechanism underpinning this result remains unknown. But one way of understanding it supposes that this compression stiffening induces the same elastic resistance in the living brain as that felt by cells subjected to substrates of different stiffness in vitro. Such compression stiffening might be attributable to increased proliferation of blood vessels within tumours or intercellular forces associated with migration.