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Why you might want to wake up a sleeping cancer cell

December 4, 2015

Waking up sleeping cancer cells might not be as bad as it sounds. Researchers at Garvan Institute of Medical Research in Sydney have used state-of-the-art microscopy techniques to watch cancer cells sleep within a living bone over a period of months. They discovered that cancer cells that snooze in the skeleton can be awakened – or left to rest – by changes in the bone that surrounds them. The discovery has great implications for new cancer treatments, suggesting novel ways of treating metastatic cancer in the bone.

In several cancers (including breast and prostate), cancer cells can spread from the original tumour site into the bone. Once there, they settle in, remaining inactive for months or even many years. Eventually, though, some of these cells can ‘wake up’ and begin to divide, forming secondary cancers (or metastases) in the bone and dramatically worsening the prognosis of cancer patients.

Researchers at Garvan set out to discover what wakes up cancer cells in the bone by using a groundbreaking technique called intravital two-photon microscopy. The team tracked the fate of sleeping multiple myeloma cancer cells in the tibia (the main bone in the long part of the leg) of a mouse and watched as a small number of the cells lodged in the tibia and ‘went to sleep’. These rare sleeping cells could be detected because they contained a fluorescent dye that was lost rapidly from dividing (wakeful) cells.

The team discovered that bone’s natural dynamic process of building up and breaking down can send signals to cancer cells to stay asleep or to wake up, and this information can be used to regulate cancer cell activity.

Professor Peter Croucher, Head of Garvan’s Bone Biology Division and the study’s lead investigator said, “Now we can see that the cancer cells are woken by changes in the surrounding bone, we can think in a whole new way about treating bone metastasis – and there are two treatment approaches in particular that have promise”.

“The first is that we could inhibit the breakdown of bone to keep cancer cells in long-term hibernation. In fact, there are already drugs that can do this, such as bisphosphonates (used to protect bone in individuals with osteoporosis), and there’s already evidence that these drugs do improve survival in breast cancer patients.”

The other more radical option is to do the opposite – to wake the sleeping cells.

“Most cancer treatments target active, dividing cells, so waking the sleeping cells should make them susceptible to those therapies – and, ultimately, could eradicate any residual disease”, Professor Croucher concluded.

The research was published today in the journal Nature Communications.

A more detailed news post is available on Garvan’s website.

The Australian Cancer Research Foundation has supported cancer research at Garvan with three grants, totaling AUD 6.13million.

Image courtesy of Garvan Institute of Medical Research. Three-dimensional two-photon image of green GFP+DiDneg cells (white arrow) and yellow GFP+DiD+cells (red arrows) localized to the bone surface, blue; scale bar, 100μm.

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