Most people who die from cancer die from metastatic disease – where tumor cells migrate from the original site and start growing tumors in other parts of the body, such as bone. Now, new research reveals fresh clues on how migrating cancer cells alter bone tissue to make it suitable for tumor growth.
The researchers hope their findings will help find new drugs that slow or stop metastasis.
Cathepsin K is normally only found in bone, where it is secreted by large cells called osteoclasts that absorb bone tissue during growth and healing.
But, until this new study, scientists have been somewhat puzzled as to why migrating cancer cells might benefit from releasing cathepsin K.
In the journal BMC Research Notes, researchers from the University of Freiburg in Germany describe how they discovered that production of cathepsin K helps migrating cancer cells survive, and possibly even thrive, in bone tissue.
Working with cell cultures, they found that cathepsin K triggers another protein that changes the microenvironment of bone tissue to make it more conducive to tumor growth.
The second protein is called matrixmetalloprotease-9 (MMP-9) – a key regulator of tumor development. This protein digests the bone matrix and allows the arriving cancer cells to establish themselves in their new environment.
MMP-9 also helps form new blood vessels to feed the growing tumor.
Senior author Prasad Shastri, a polymer chemist and professor in the Institute for Macromolecular Chemistry at Freiburg, says it seems that when cancer cells arrive in bone tissue, they have a number of tools that help them change their environment and grow into new tumors. He concludes:
“Further studies are, however, needed to see how this interplay between cathepsin K and MMP-9 actually plays out in vivo and how it promotes tumor aggressiveness and metastasis.”
Nevertheless, Prof. Shastri says the findings add weight to the idea of targeting cathepsin K to limit bone metastasis. Should they be confirmed in live tissue, then they offer a framework for finding drugs that specifically block cathepsin K’s ability to activate MMP-9.
Cancer has a major impact on society around the world. It is one of the leading causes of disease and deaths worldwide. According to the World Health Organization (WHO), in 2012, there were 14 million new cases of cancer and 8.2 million deaths.
The number of new cancer cases per year is expected to rise to 22 million within the next 2 decades. Most deaths from cancer result from metastases.
Meanwhile, Medical News Today recently learned text books about bone repair will have to be rewritten after researchers showed bone fractures do not heal the way we thought. Contrary to current thinking, it is the breakdown of fibrin, and not its presence, that is essential for fracture repair. Fibrin is a protein involved in blood clotting.