Most people die of metastatic disease, in which the tumor spreads from the primary site to other parts of the body. Although scientists know how the cancer cells make their way to different parts of the body, it remains unknown why some form new tumors in decades, while others never do.
A team of researchers at the Montefiore Einstein Comprehensive Cancer Center has developed a breakthrough to understand it. They have identified a natural immune response in mice that prohibits cancer metastatic cells from growing into new tumors when they spread. This study, as published in Cell, could lead to new treatments for metastatic cancer.
“Preventing or curing metastases is the biggest challenge in cancer,” said Dr. Julio Aguirre-Ghiso, the study’s lead author and director of MECCC’s Cancer Dormancy Institute. “We believe our findings may lead to new therapies to fight metastatic disease.”
When tumor cells disseminate, they are called disseminated cancer cells. While some DCCs readily form tumors, others enter a state of dormancy. “We’ve long wondered why some DCCs stay dormant for years without causing new tumors,” said Dr. Aguirre-Ghiso. “Now we think we’ve found the answer.”
The team worked with metastatic breast cancer. Using three mouse models, they determined when DCCs reached the lungs, they entered a dormant stage at the hands of immune cells referred to as alveolar macrophages. These are the main guards of the lungs against noxious particles, including bacteria and pollutants.
As Dr. Aguirre-Ghiso explained, “Alveolar macrophages also play an important role in maintaining DCCs in a dormant state. They interplay with DCCs and release a protein called TGF-b2, which contributes to keeping them in a dormant state.” These macrophages are present from early development onward and stay in the lungs for life.
Researchers observed that ablation of alveolar macrophages in mice caused. There is increased activation and tumor formation by DCCs. This therefore shows the importance of these macrophages in the maintenance of DCCs in their dormant state.
They also found that as DCCs become more aggressive, they become resistant to these same signals, which promote their dormancy. This resistance allows some DCCs to “wake up” and form metastatic tumors.
He believes this will lead to therapies supporting the macrophage signals that keep the DCCs in a dormant state. And prevent them from awakening and spreading.
ANI
