Cells in tough tissues 'more vulnerable to cancer-causing genetic mutations'

Cells that are "squeezed" inside tough tissues such as lung or bone are more vulnerable to cancer-causing genetic mutations, a study has found.

Others with "soft" homes, including the brain and bone marrow, tend to exhibit fewer genetic abnormalities, say researchers.

The explanation is partly the stress forces that act on cells when they move and divide, they claim. In a more rigid structure, these can inhibit repairs to defects in DNA.

Tumours arising in stiff tissues exhibited mutation rates and chomosomal variations 100 times higher than those seen in soft tissues, the US scientists discovered.

Dr Jerome Irianto, from the University of Pennsylvania, said: "Basically, we hypothesise that stiffer tissues with their denser matrix and smaller constrictions cause more nucleus deformation that damages the nucleus."

To investigate the effect, the researchers set up an experiment in which cancer cells were made to migrate through thin plastic filters pierced by tiny holes.

When the cells had to force their way through three micrometre-wide holes, they accumulated more DNA damage than when they passed through larger eight micrometre-wide holes.

Further experiments showed that DNA repair proteins were prevented from doing their job by too much squeezing.

"What we are addressing right now is whether this constricted migration with molecular damage and segregation will translate to genomic instability, which is a hallmark' of cancer, Dr Irianto added.

"Cancer needs to invade to spread, and that invasion could itself cause mutations."

The research was presented at the Biophysical Society's annual meeting in Los Angeles.

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