Dormant cancer cells in bone tissues can be awakened by changes happening in their surroundings, according to scientists from the Garvan Institute of Medical Research, Australia. These new findings, published in the journal Nature Communications, suggest that activating the sleeping cells can help treat secondary cancers.
For the first time ever, researchers have observed slumbering cancer cells in living bone tissue using intravital two-photon microscopy. It was found that these sleeping cells can be left to themselves, or awakened: the researchers showed that the breaking down of surrounding bone tissues would randomly put an end to the ‘sleeping state’ of some of the cells.
The findings are hoped to boost research in treating metastatic cancer that spreads in the bone. Many forms of cancer can propagate from the main tumours to the bones where they remain inactive for some time, only to wake up months or years later when they are triggered to divide into more cells, thereby bringing about secondary cancers known as metastases. This constitutes a worsened condition that becomes increasingly difficult to treat. Therefore, being able to point out the cause of the activation following the long sleep is important for treatment.
The scientists followed the progress of the sleeping cancer cells in the tibia, the main bone in the leg, of a living mouse. When they inserted cells from a form of cancer called multiple myeloma – that affects blood cells and the bone – into the mouse, they found that the cells entered the tibia and “slumbered” on there itself. The disappearing cells could only be identified because they bore a fluorescent dye. The scientists were able to find out the cause of the reactivation because they could observe the very same cells in the tibia of the very same mouse for a long period of time – an unprecedented feat.
One of the observations was that only some of the many dormant cells would wake up, and they would do so at different times. Some were even deactivated again after being woken up. The great difference in the behaviour of the myeloma cells indicated that they were being controlled from an external signal – one that originated outside the cell.
The “wake-up” call apparently was made by dynamic processes occurring in the bone (which is normally constantly being built up and broken down): a close link with inactive bone-lining cells found on an inner layer of the bone would cause the cancer cells to remain asleep. The myeloma cells would then be woken up by the activation of another type of cells known as osteoclasts known to break down bones; osteoclasts might be bringing about physical changes in the environment of the cancer cells, thereby putting an end to their sleep. The authors describe this action as “throwing them out of bed”. This process would be random, according to the researchers, such that a cancer cell being at the “wrong place at the wrong time” would be awakened.
A treatment methodology based on the new information has been suggested: the action of osteoclasts breaking down the bones could be inhibited in order to keep the cancer cells ‘in bed’ so that secondary cancers do not even arise. Existing drugs used to alleviate osteoporosis can already do that. Or, an alternative way would be to wake the sleeping cells by activating the osteoclasts so that they are made vulnerable to therapies that essentially target active, dividing cancer cells.