Most breast tumors are stiffer than surrounding tissue--it's how they were first described in ancient Egypt, and it's how they are still routinely caught today. Not all cancer cells are responsive to stiffness, but those that are become mechanically conditioned, and it changes how thousands of genes are turned on or off. Intriguingly, mechanical conditioning can be non-genetically inherited as cancer cells proliferate via a mechanism called "mitotic bookmarking" hijacked from stem cells.
In the experiment shown below, we sorted breast cancer cells based on whether they had lost their mechanical conditioning (left panel) or retained mechanical conditioning long-term as mechanical memory (right panel). These time-lapse movies show the cancer cells invading through collagen in 3D using enhanced depth-of-focus imaging. Mechanical memory instructs cancer cells to invade, spread, and seek out the bones in patients.
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