How Cancer Cells Adapt to the Environment of the Bone

Researchers evaluate how cancer cells adapt and survive in a new bone environment.

A recent discovery regarding tumor development may lead to a new target for future cancer drugs.

Cancer cells that travel to the bone obtain a unique characteristic: they begin to express the protein cathepsin K.

Researchers from the University of Freiburg and the BIOSS Centre for Biological Signaling Studies now understand why it is important for the migrating cells to produce this protein. The scientists discovered that the protein activates another protein, which then helps cancer cells to alter their microenvironment so that they are able to metastasize into tumors.

As a tumor develops, the chances of survival in the patient severely decrease. Cancer cells that leave the tumor and spread to other areas, such as the lungs and bones, begin to express cathepsin K. Cathepsin K is primarily found only in the bone and is secreted by osteoclasts. These cells resorb bone tissue to maintain, repair, and remodel the bone.

Polymer chemist professor Prasad Shastri, PhD, and pharmacist Jon Christensen discovered that the production of cathepsin K by traveling cancer cells may promote its ability to survive in the bone environment. Cathepsin K activates matrixmatalloprotease-9 (MMP-9) in cell cultures, which is one of the key regulators of tumor development.

By digesting the bone matrix, MMP-9 can allow the arriving cancer cells to adapt and survive in the new bone environment. MMP-9 also activates certain factors that promote new blood vessel formation, necessary for bringing nourishment to the tumor cells.

Therefore, when cancer cells move to bones they have multiple avenues of adapting to the new environment and developing into tumors.

“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,” said Shastri. “Nevertheless, this novel protease network paradigm might be explored as a therapeutic target in the future.”