Breast cancer cells spread by digging their escape route
Breast cancer cells puncture holes into neighbouring tissues and crawl though the spaces they create to spread around the body, according to research published in the Journal of Cell Biology.
Scientists at Cancer Research UK’s Beatson Institute in Glasgow discovered that there are high levels of a protein called N-WASP in breast cancer cells.
The protein helps form branches with sharp points on the cell surface by rearranging the cell’s internal ‘skeleton’, made of a protein called actin. Actin is essential in all cells for structural support, movement and shape changes.
The branches with sharp points – called pseudopodia – can grab onto and poke holes into the extracellular matrix, the supporting tissue in-between cells. And the team showed that enzymes attach to the protrusions and dig into the extracellular matrix, creating larger spaces.
Cancer cells invade their surrounding environment by a combination of pushing and pulling into the newly created spaces – movement which is captured for the first time in 3D on video.
The scientists showed that removing N-WASP from cells resulted in much blunter protrusions, to which fewer enzymes became attached. This reduced the ability of the cells to puncture their surrounding extracellular matrix and spread.
Lead author, Dr Laura Machesky, at Cancer Research UK’s Beatson Institute in Glasgow, said: “Our exciting results reveal a completely new process by which cells can break away from a tumour to invade surrounding spaces and spread around the body. We found that cells assemble specialised structures, with the ability to hold onto the surrounding tissue matrix and dig tunnels into it, which they can then crawl through.
“Our research suggests that N-WASP is a promising target for the development of drugs to combat cancer spread. We were particularly intrigued because blocking N-WASP activity didn’t affect healthy cells, so we think that N-WASP could be specifically targeted to prevent cancer spread.”
Dr Julie Sharp, Cancer Research UK’s senior science information manager, said: “This important research reveals fresh understanding of how cancer spreads, which will help scientists to translate discoveries into effective treatments to beat cancer.
“Most cancer deaths are caused when cancer cells travel to new sites within the body and grow as secondary tumours so there’s an urgent need to find a way to stop this happening.
“We’re funding groundbreaking lab research into how cancer cells move around the body as well as important clinical trials which aim to combat the advanced disease. Finding the best ways to tackle cancer spread will save thousands more lives every year.”
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Machesky, L. et al. N-WASP coordinates the delivery and F-actin mediated capture of MT1-MMP at invasive pseudopods to drive matrix remodelling and cancer cell invasion. (2012) Journal of Cell Biology. doi: 10.1083/jcb.201203025