Ninety percent of cancer deaths are related to metastasis, making research to understand its causes and identify potential ways to prevent it very important. In a new Nature Communications study, scientists at the Georgia Cancer Center at Augusta University report that cancer can hijack a certain type of immature immune cell to help it spread.
The research focused on myeloid-derived suppressive cells (MDSCs), which come from bone marrow. Present in low levels in healthy patients, these cells differentiate and expand in response to pathological situations, such as a bacterial infection or tumor. MDSCs are found in high amounts in mouse models and patients with cancer, and their role in cancer metastasis has become an active area of research. MDSCs are now known to be a key obstacle in developing successful immunotherapy treatments. They also appear to be involved in angiogenesis, or helping tumors form the blood vessels they need to survive.
It’s believed that tumor cells about to metastasize emulate stem cells so that they can free themselves from the primary tumor and more easily travel to a new area of the body. Once migrated, they revert to a state that enables them to settle in the new location.
The new research demonstrates that MDSCs are involved in both parts of metastasis. One type, monocytic MDSCs, helps tumor cells become stem cell-like. Another type, granulocytic MDSCs, helps cancer cells revert to their initial state, take up residence and grow.
“There is a very intricate balance in the immune system that is usually anti-tumorigenic, meaning it eliminates tumors, but in some cases, if this balance is altered, these cells may actually help tumors grow and develop into full-blown metastatic disease,” senior author Dr. Hasan Korkaya said in a press release.
Tumor cells appear to be using cytokines to hijack MDSCs for metastasis. Cytokines are small signaling proteins, typically secreted by the immune system to influence other cell types. However, tumor cells can also secret cytokines, sending a message to MDSCs to support their spread.
The research team is now exploring ways to make MDSCs fight rather than support tumors, including by targeting cytokines found in high levels in metastatic cancer.
- Highly Systemic Metastatic Cell Lines
- Human Bone Marrow Mesenchymal Stem Cells
- Cytokines and Chemokines