Researchers found that cancer cells migrating to other parts of the body produce a certain protein that lets tumors develop more easily in bones.
In a study published in the journal BMC Research Notes, researchers from the BIOSS Centre for Biological Signalling Studies and the University of Freiburg showed that cancer cells migrating to the bone develop a unique trait wherein they produce cathepsin K, a protein. Jon Christensen and Prasad Shastri discovered, however, that cathepsin K promotes the activation of another protein called matrixmetalloprotease-9 (MMP-9), which aids cancer cells in achieving the perfect environment for them to thrive in and develop into tumors.
If a tumor spreads, a cancer patient's chance of survival drastically drops. Cancer cells have the ability to leave the primary tumor and travel around the body, setting up home in organs like bones and lungs. Cathepsin K is mainly found in the bones released by osteoclasts, which reabsorb bone tissue to care for the bone.
In cell cultures, cathepsin K was found to activate MMP-9. As key regulator for tumor growth, it has the ability to digest bone matrix, allowing cancer cells to easily adapt and survive even though they are in a new environment. Additionally, MMP-9 promotes the formation of new blood vessels, ensuring cancer cells receive the nourishment they need to turn into tumors. As such, by the time cancer cells get to the bone, they already have the tools they need to thrive.
Christensen and Shastri said though that further studies will have to be carried out to determine the exact relationship between cathespin K and MMP-9 and how tumors grow and spread.
MMP-9 is actually involved in a number of biochemical and physiological processes. It is first secreted as an inactive enzyme then a cysteine from the N-terminal pro-domain binds to MMP-9's zinc atom, maintaining latency. To activate the protein, the cysteine-zinc interaction must be disrupted. This will expose the catalytic site, allowing for MMP-9 to activate. This is how cathepsin K works to activate the protein.
"Nevertheless, this novel protease network paradigm might be explored as a therapeutic target in the future," the researchers added.
The study received funding support from the German State and Federal Governments' excellence initiative. Additional aid was provided by the University of Freigburg and the German Research Foundation for article processing.
