Mechanisms Behind Cancer Metastasis

Cancer cells hijack immature immune cells to help the disease successfully spread throughout the body.

In a study published in Nature Communications, investigators found that cancer uses myeloid-derived suppressive cells (MDSCs) derived from the bone marrow to act as a support system to successfully metastasize.

“These cells are essential to successful cancer metastasis,” said corresponding author Dr Hasan Korkaya in a press release.

Prior research has shown that high levels of MDSCs in mouse models and patients with cancer are good at suppressing the immune response. However, their role in enabling tumors to spread successfully is beginning to emerge.

Scientists believe that when tumor cells are about to leave the primary site, they become stem-like to free themselves from the primary tumor, and more easily migrate to a new area. Once they arrive at a new location, they revert to a state that allows them to stay and thrive.

The results of the new study show that commandeered MDSCs aid monocytic MDSCs and granulocytic MDSCs. Monocytic MDSCs help the tumor cells complete the stem-like transformation, while granulocytic MDSCs helps to revert the cells, allowing them to settle in and grow.

MDSCs appear to receive their direction from cytokines secreted by the tumor, according to the study.

“They are being schooled toward facilitating tumor cell growth and metastasis,” Korkaya said. “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.”

Prior to the current study, Korkaya had a strong suspicion that a concoction of certain cytokines would allow tumors to harness MDSCs suppressive power to their advantage. In early work, Korkaya was among the first to show that antibodies that eliminate cytokine IL-6 significantly reduced metastasis of breast cancer in mice.

Currently, the investigators are exploring ways to reschool the large volume of wayward cells to fight rather than support the tumors.