How breast cancer cells spread decoded

Breast cancer cells spread to different parts of the body by sliding around other cells blocking their escape route out of the original tumour, researchers, including one of Indian-origin, have found.
The spreading of cancer cells from one part of the body to another, a process known as metastasis, is the leading cause of death among cancer patients, researchers said.
The findings explain why some cancer cells may be more metastatic than others, they said.
"We demonstrate a quantitative ruler for measuring how well a cell is able to slide. By putting numbers to this cellular behaviour, we can not only discern which pathways regulate sliding, but also how much," said Anand Asthagiri from Northeastern University in the US.

"This opens the door to finding the most powerful drivers of sliding behaviour and strategies to curb this invasive behaviour," said Asthagiri.
"Keep in mind that each cell is 10-15 micron wide and is finding a way to slide past a neighbour, also 10-15 micron wide. And they do all this on a track that is only 5 micron wide," he added.

"How they physically squeeze, extend and wrap around is really remarkable and a fascinating biophysical problem. We were very interested in sorting out the mechanics and regulation of how cells accomplish this, and why cancer cells are particularly adept at it," he said.

Researchers stamped a glass surface with micropatterned lines of fibronectin protein, and then used time-lapse microscopy to study collisions between pairs of cells deposited on the adhesive fibres.
On micropatterns that were only 6 microns or 9 microns wide, mimicking conditions in the tumour environment, 99 per cent of normal breast cells stopped and reversed direction upon physical contact with another cell, researchers said.
By contrast, about half of metastatic breast cancer cells responded to collisions by sliding past the other cell, maintaining their migratory path along the protein track, they said.
The normal breast cells were much more likely to slide past other cells when the researchers either increased the micropattern width to 33 microns, or reduced levels of E-cadherin - a sticky membrane protein that binds cells together, researchers said.

Meanwhile, increased levels of E-cadherin diminished the sliding behaviour of metastatic breast cancer cells, they said.
Additional experiments revealed that PARD3, ErbB2, and TGF beta - proteins implicated in metastasis - cooperate to regulate cell-sliding behaviour, researchers said.
Taken together, the findings demonstrate the key role of cell sliding in supporting metastasis, and the molecular pathways that allow this to happen, they said.
The findings were published in the Biophysical Journal.