Researchers have shown that cancer cells that are dormant in the skeleton can be awakened by changes in the bone that surrounds them.
Researchers have used state-of-the-art microscopy techniques to watch cancer cell sleep within living bone over a period of months. These findings suggest new possibilities for treating metastatic cancer in bone.
In several cancers, cancer cells can spread from the original tumor site into bone. Once the cancer cells spread to bone, they can remain inactive for months or even many years. Eventually however, some of these cells can “wake up.” Once they wake up they begin dividing, forming secondary cancers in bone and dramatically worsening the prognosis of cancer patients.
In the study, researchers tracked sleeping cancer cells in the tibia of a living mouse. They introduced cells from multiple myeloma into the mouse and watched as a small number of the cells lodged in the tibia and went to sleep. These rare sleeping cells were able to be detected because they contained a fluorescent dye that was lost rapidly from dividing cells.
Looking at a long bone like a tibia, rather than the skull, allowed researchers to watch the same sleeping cancer cells in the same bone, in the same mouse, over a long period of time.
Studying the same set of cells over a period of months gave vital clues about what caused them reactivate. Researchers were able to observe numerous dormant cells, yet only some get woken up, and those that do wake, wake at different times. Researchers even observed some cells that woke up then go back to sleep again.
The fact that these cells behave so differently, although they all come from the same cancer cell line, gave researchers an indication that it is a signal from outside the cells that is controlling when they wake.
The next challenge was to determine the exact nature of the wake-up call from bone.
These findings allow researchers to thinking in whole new way about treating bone metastasis. There are currently two treatment approaches in particular that have promise.
The first treatment approach is to inhibit the breakdown of bone by osteoclasts so cancer cells stay dormant.
The second treatment approach is to do the complete opposite, wake the sleeping cells by activating osteoclasts. Most cancer treatments target active, dividing cells, so waking the sleeping cell should make them susceptible to those therapies.